Kpc cell line. All cells and organoids were routinely tested for Mycoplasma using PCR (Universal Mycoplasma Detection Kit, ATCC, 30–1012K). Consistent with results from The KPC pancreatic adenocarcinoma cell line, which was derived from a spontaneous tumor originating in a transgenic Kras LSL-G12D/+; Trp53 LSL-R172H/+; Pdx-1-Cre mouse (B6/129 background) , [16, 17] was cultured in DMEM, containing 10% FBS, 100 U mL −1 penicillin, 100 µg mL −1 streptomycin, 2 × 10 −3 m l-glutamine and 1 × 10 −3 m sodium MC38, CT26, LLC, and KPC cell lines were grown in DMEM supplemented with 1x pen/strep, 10% FBS, 10 mM HEPES, 1x nonessential amino acids, 1x Glutamax, and 1x sodium pyruvate. To evaluate and compare the tumor-killing potential of TAMs and T cells from KPC mice treated with OV-GFP or OV-BiTE, TAMs were isolated from the tumors of treated In this study, we describe the successful establishment and characterization of three cell lines derived from two (PDAC) mouse models. MRTX1133 inhibited ERK1/2 phosphorylation and cell viability in KRASG12D-mutant cell lines, with median IC50 values of ~5 nM, and demonstrated >1,000-fold selectivity compared to KRASWT cell lines. Similar substantial variability was seen in the other parameters, including baseline DNA damage, plating efficiency, and ploidy. Based on the relative success of the MPACT trial, combinations of gemcitabine liposomes with I previously transfected (by using lipofectamine) rat hepatoma cells with my target gene and used 10%DMEM+PS+500 μg /ml G418 to obtain clones that were expressing my target gene. :NM-YD04-TG01. Green circles: six carriers of heterozygous mutations in either BRCA1 or BRCA2. First, the oncogenic potential of the 91 MYC binding partners was tested in the murine KPC cell line harbouring oncogenic mutations in KRAS and p53,34 because this cell line engrafts in C57BL/6J mice and forms MYC-dependent tumours. Mouse models are essential to studying pancreatic cancer and there are numerous models which would be useful to Mouse-derived cell lines. Cells were grown in DMEM containing 10% fetal calf serum supplemented with penicillin/streptomycin and L-glutamine (complete medium) at 37°C in 5% The KPC cell line was originally obtained by S. 100 μl of this mixture (1000 cells per well) was plated in 96-well plates (Nunc), whose wells had been previously coated with a bed of GFR-Matrigel to prevent The cell line was transfected with pLVX-IRES-Neo- full-length OVA plasmid to generate OVA + Luc + GFP + KPC cell line. It is the most common type of pancreatic cancer. The KPC PDA tumor cell line was developed from a KPC mouse as described previously. Cell lines culture, cell purification and differentiation in vitro. Luc, Panc02, BXPC3, Capan-02 and cells were plated on a 96 well plate and treated with varying concentrations Lewis and KPC cell line were grown in Dulbecco’s Modified Eagle Medium (DMEM) (supplemented with 10% fetal bovine serum, 100 U/mL penicillin, and 100 U/mL streptomycin). ˜e KPC cell line was provided by Prof. Both cell lines were more aggressive in their ability to form tumors when compared to other pancreatic cancer cell lines, and showed constitutive The orthotopic mPA KPC-Luciferase tumor model was well established by implanting tumor cell line into pancreas of B6 wild type mice and the tumor growth was traced by in vivo imaging. Our study compiled 15,660 bla KPC-positive isolates globally over the past two decades. Taken together our data, with the observation that serum level of GM-CSF is significantly higher in colon adenocarcinoma patients [ 31 ], suggest that GM-CSF might KPC tumor-derived cell line (KPC cell) was separated from spontaneous KPC tumor and was identified as a genotype of Kras G12D/+; Trp53 R172H/-by standard PCR. derived from pa ncreatic tumo rs of C57BL/6-Trp53. 10 μL concentrated viral particles and 8 μg/mL polybrene were added into 1m fresh medium. KPC mice emerged to be better suited for studying long-lasting cancer pain that emerges over a slow course of tumor progression. Gemcitabine was dissolved in Burrack et al. J. Autologous T cells were isolated from human pancreatic cancer tissues and expanded in the DMEM/F12 There was a wide variation in the intrinsic radiosensitivity of cell lines, with cell line Mean Inactivation Doses (MID) ranging from 1. we characterized the effects of implanting a pancreatic tumour cell line from a syngeneic C57BL/6 KRAS G12D P53 R172H Pdx-Cre +/+ (KPC) mouse. 1 × 10 6 cells per mouse) into the pancreas of 6-week-old C57BL/6 mice. You may also like. :NMC-230049. For the 8661 cell line (gift from Prof. The cell biology collection includes more than 4,000 continuous cell lines available by species, tissue/disease types, and signaling pathways. 0 mM) with or without supplementation with either mouse serum albumin (KPC) or human serum albumin (MP2) at 3% per volume and proliferation capacity The KPC cell line was a gift from Dr. Analysis of Tumorigenesis in C57BL/6 mice(n=6). The murine pancreatic cancer cell line KPC FC1199 (kindly provided by the Tuveson Laboratory, Cold Spring Harbor Laboratory) was isolated from PDAC tumor tissues of KPC (Kras G12D/+; Trp53 (A) 28 non-ovarian cell lines; (B) 16 ovarian cell lines. Analyzing Vps4b and Rnf31 in melanoma and breast cancer cell lines, moreover, indicate a partial conservation of this phenotype in other cancer entities, with loss of Rnf31 also KPC-derived murine pancreatic cancer cell line was obtained from Prof David Tuveson (Cold Spring Harbor, USA). cDC1 dysfunction is The KPC cell line was a gift from Dr. Cell lines were derived from primary KPC tumors and cultured in Dulbecco’s modified eagle medium (Hyclone) with 10 % fetal bovine serum (FBS) and 1 % penicillin/streptomycin. HEK 293T To determine whether mtp53 regulates the innate immune signaling pathway, we initially performed short hairpin RNA (shRNA) knockdown of mtp53 in the human breast cancer cell lines BT549 (p53R249S) and MDA-MB-231 (p53R280K) and the pancreatic cell lines MIA PaCa-2 (p53R248W) (human) and KPC (p53R172H) (mouse). Orthotopic Tumor Implantation and Treatment. A mouse KPC cell line expressing human Claudin 18. In addition to the KPC mouse and cell-line models, we also provide various spontaneous tumor model resources for preclinical drug development. Input, left The KPC cell line was thus suitable for subsequent experiments. The cells were cultured in KPC 4662 Rab27a 3. The TROMA-I antibody against cytokeratin-8 developed by Brulet P et al. KPC cancer cells were isolated from a 5-month-old LSL-Kras G12D /LSL-Trp53 R172H /Pdx1Cre GEMM. 1a) and in a panel of PDAC cell lines The KPC-Luc-4580 cell line demonstrated a greater number of FFU/mL, size of plaques, and cell lysis compared to PANC02-Luc and SUIT2 cells, showing a significantly higher number of FFUs and cell b Western Blot analysis of KPC cell lines after TNF treatment (100 ng/ml) for active NFκB signaling (phospho-p65; upper panel) and cleaved caspase 8/caspase 8 (bottom panel). H. Gene expression profiling has contributed significantly to our understanding of this heterogeneity at a molecular level, refining taxonomy based on simple measures such as histological type, tumour grade, lymph node status and the presence of predictive markers like oestrogen receptor and human By mimicking this observation in PDAC cell lines, 5 × 10 5 PANC-1 cells or 1 × 10 5 KPC cells dissolved in PBS were injected subcutaneously or orthotopically into 6–8 week old HPAC is the first reported human pancreatic adenocarcinoma cell line to express a functional glucocorticoid receptor. Isoenzyme analysis is used to confirm the identity of the species of a cell line. Moreover, Gemcitabine or combined with CD40 agonist presented significant tumor growth inhibition in B6 bearing mPA KPC -Luciferase orthotopic mouse models. Metastatic disease is already found in most patients at The ATCC® KPC Strains Panel (ATCC® MP-24™) comprises four strains confirmed to carry the blaKPC gene conferring resistance to carbapenem antibiotics. David Tuveson (Cold Spring Harbor, Cold Spring Harbor, NY) and treated as for the 8661 cell line. 14(2020) We next used the KPC-derived PDAC cell line KPC105 and conducted a similar study in vitro. The KPC cell line was derived from a Thick arrows indicate macrophages that contain Lucifer Yellow spread from KPC cells (thin arrow) around them. , Grand Island, NY). David Tuveson (Cold Spring Harbor Laboratory). 2) was first established using the modified HSV-1-susceptible mouse KPC cells. Treatment of PDAC-bearing mice with clodronate liposomes, an agent that chemically depletes macrophages, did not impact macrophage subpopulations in the local tumor microenvironment (TME). Cell lines and mice. The UN-KPC-961 cell line was derived and characterised in our laboratory (Torres et al, 2013) from a primary tumour developing in KPC (LSL-Kras G12D KPC cell lines (KPC-344, KPC-22, KPC-105) established from KPC spontaneous mouse model were injected subcutaneously in C57BL/6J mice. This tumor was captured for single-cell RNA-sequencing followed by CNV analysis and cell type annotation. 4 mM, and MP2 shCAV1 = 1. This coincided with the loss of bioluminescence signal over the tumor region. 95% of all pancreatic cancers are PDA. The immortalized CAF cell line isolated from KPC tumors was a kind gift from Dr. 8, 9 Specifically, the 4662 cell line induces less severe cachexia in mice compared with the KPC cell line. 65 Gy in Lig4 −/− cells. F. The characterisation of the KCI-313 cell line is detailed in Figure S1. 2 mM, KPC-CAV1 fl/fl = 0. 79 GFP-labeled KPC cells were generated as described previously. To determine the effect of Ant-08 on the growth of PDAC cell lines in-vitro, MT5, KPC. To determine whether mtp53 regulates the innate immune signaling pathway, we initially performed short hairpin RNA (shRNA) knockdown of mtp53 in the human breast cancer cell lines BT549 (p53R249S) and MDA-MB-231 (p53R280K) and the pancreatic cell lines MIA PaCa-2 (p53R248W) (human) and KPC (p53R172H) (mouse). Jing Establishing models of hepatic and pulmonary metastatic pancreatic ductal adenocarcinoma. Other murine cell lines also express the retroviral gp70 mRNA and give rise to tumor gp70-specific T-cell responses; such cell lines include the BALB/c-syngeneic 4T1 mammary carcinoma cell line Here, we report a high level of TAM infiltration in human and mouse pancreatic ductal adenocarcinoma (PDAC) models and that the targeting of proliferating F4/80+ macrophages facilitated cytotoxic CD8+ T-cell Summary. This cell line retains the mutations seen in the parental KPC murine model. doi: 10. 22 Cells were cultured with Dulbecco’s Modified Eagle Meidum DMEM (Gibco #11965092) with 10% fetal bovine serum (FBS) Lewis and KPC cell line were grown in Dulbecco’s Modified Eagle Medium (DMEM) (supplemented with 10% fetal bovine serum, 100 U/mL penicillin, and 100 U/mL streptomycin). We treated KPIC and KPC cells with gemcitabine and Abraxane in vitro. To establish directly comparable lung and liver PDAC metastasis, we utilized a murine pancreatic adenocarcinoma cell line driven by Kras and Trp53 mutations (KPC) [] injected into the two most common visceral sites of metastatic disease, liver, and lung. A A Kras LSL-G12D; Trp53 LSL-R172H; Pdx1-Cre spontaneous tumor mouse model was used to derive the KPC cell line. 5 μM final concentration, Sigma), and Growth factor-reduced Matrigel (GFR-Matrigel, 10% final concentration). Cell extracts were then subjected to the same Description: Established cell line is derived from a KPC mouse and represents a model of pancreatic ductal adenocarcinoma (PDA). Disease 3. Splenic T-cells were harvested from murine spleens as described in section 2. Together, these findings suggest not only We found that N6F11-treated KPC cells protected mice from tumor rechallenge and that this long-distance protection was curtailed by the administration of αCD8 or αHMGB1 (fig. A. PDAC cell lines used in this study included PANC02 and KPC. The result showed that malignant cells expressed ductal markers (such as KRT18 and KRT19) and exhibited stronger CNV features, supporting that the KPC cell line was PDAC tumor cell. Pancreatic ductal adenocarcinoma (PDA) is a type of exocrine pancreatic cancer. If left untreated, mice with hemispleen tumor Only the KPC cell line demonstrated a response to liposomal treatment similar to that expected of an ideal TSL. Raghu Kalluri’s laboratory (MD Anderson Cancer KPCM and KPC cell lines or organoids were established from tumor tissues of pancreatic ductal adenocarcinoma derived from KPCM and KPC mice [32,33,34]. 10 For animal experiments, KPC cell lines were trypsinized and resuspended in phosphate buffered saline/Matrigel in a 1:1 ratio. The Figure 1. Cell culture. Murine KPC cell lines were received from the Tuveson Laboratory and maintained in RPMI1640 with 10% FBS and penicillin/streptomycin at 37°C with 5% CO 2. 2 cells but significantly inhibited cell growth in co-culture with mouse spleen lymphocytes (Figures 4A and 4B). All of the cell lines used in this study were purchased from ATCC and were authenticated by The Cell Bank of Type Culture Collection of the Chinese Academy of Science (CBTCCCAS) with STR profiling. Kimmelman. This cell Antibodies were diluted 1:100 in FACS buffer (PBS + 2. Yet, using Panc02 cell lines, the efficacy of generating tumor in For generation of clonal organoid lines, KC and KPC pancreas organoids were dissociated into single cells and seeded into 6 well plates. Determination of sex in the KPC cell line. Flow cytometric enrichment of CD326 + /CD31 − /Fsp1 − /CD45 − cells was performed. 5 % FBS) and cells were stained at RT in the dark for 20 min before acquisition using an LSRFortessa X-20 flow The fold-change in gene expression of Amylase and CK19 mRNA in cancer cell lines were compared relative to mRNA levels extracted from The KPC mouse is an established and clinically relevant model of pancreatic ductal adenocarcinoma (PDA) which develops many key features observed in human PDA including The above table contains some pancreatic cancer mouse models, the expression of these genes is driven by pancreas-specific Cre alleles. PANC-1 and KPC cell lines were treated with different concentrations of HNK (0, 2. I previously transfected (by using lipofectamine) rat hepatoma cells with my target gene and used 10%DMEM+PS+500 μg /ml G418 to obtain clones that were expressing my target gene. The results demonstrated that the PD-L1 levels in KPC-Tnfr2 knockdown cells were reduced significantly (figure 3I-N). Five mice per group were used to test each KPC cell line using both mouse models, respectively. (C) Drugs targeting both L3. Cells were maintained in DMEM supplemented with 10% FBS and antibiotics and cultured at 37°C and 5% The B2CA-SBS signature occurs in 5 of 5 KPCBnull PDAC cell lines, consistent with the biallelic inactivation of Brca2 (Figure 1B). In contrast, KPC cell lines mutant for Vps4b or Rnf31 displayed a strong growth disadvantage under immune attack, leading to an outgrowth of GFP + control cells (Fig. In the CRISPR-modified cell lines, The KPC cell line (line 4662) was a kind gift from Dr. Unexpectedly, this signature also occurs in 2 of 5 KPC cell lines and in 7 of 7 KPCBhet cell lines (Figure 1B). Cells were stained for H-2K b 48 hours after infection, and cells with low levels of H-2K b were collected by FACS. This result was confirmed in BxPC-3-TNFR2 knockdown and SW1990-TNFR2 cell lines (online supplemental figure 7A). However, recent reports showed that KPC cell lines are poorly immunogenic due to their similar growth rates in immunodeficient mice and in immunocompetent mice . KPC cells have We observed that early-passage cells consisted of two cell types: After the 3rd passage, we obtained a cell line with epithelial characteristics. T cells accumulate intratumorally yet rapidly exhaust. No sex differences Compared to Panc02 cell lines, KPC cell lines and other KC-derived cell lines are better representations of the human PDAC disease as they share more genetic mutations. During cell culture, cells were kept in an incubator at 37°C with 5% CO 2. 10 For animal experiments, KPC cell lines were trypsinized and resuspended in phosphate buffered saline/Matrigel in a 1: KPC mice-derived PDAC cell line FC1199, referred to as KPC, was a generous gift from Professor Jing Xue (State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji UN-KPC-961 was the most resistant line used. em4(LSL . 2022 Aug 24;11(17):2634. Derived from site: In situ; Pancreas; UBERON=UBERON_0001264. However, further investigation using both BrdU and Ki67 to evaluate Morphology of KPC cell line. 6). After 30 passages, the cell morphology and growth were stable. F. We also analyzed amino acid levels in our experimental models. , 2010). Both INY-05-040 and GDC0068 target all three AKT isoforms and there is always a potential for off-target effects from pharmacological agents [19, 20]. B Body weight was simultaneously checked. Cell Line: KPC-Tg(luc)/smoc. Tumor variants defective in IFNγ-inducible Tap1 and MHC class The cell line has been screened using the membrane filtration testing methods to confirm the absence of aerobic, anaerobic and fungi microorganisms. Cells. Triple re- The KPC cell line 95775 (mycoplasma-free) was generated from a B6-KPC tumor bearing mouse. Here, we report that cDC1 dysfunction instead develops in the earliest stages of preinvasive pancreatic intraepithelial neoplasia (PanIN) in the Kras LSL-G12D/+ Trp53 LSL-R172H/+ Pdx1-Cre–driven (KPC) mouse model of pancreatic cancer. , 2004; Ikeda et al. The antigen can be recognized by T cells from OT‐I mouse due to the transgenic inserts of Tcra‐V2 and Tcrb‐V5 genes. , To understand the possible functional role of HAPLN1 in PDAC, we overexpressed HAPLN1 in a murine PDAC tumor cell line derived from KPC (Kras G12D; Trp53 R172H; Elas-CreER 28) mice. Both cell types were maintained in Dulbecco's modified eagle medium (DMEM) containing 10% fetal bovine serum (FBS) and 1% Cells were trypsinized and counted every 24 h for 5 days. In addition, there are marked growth differences between the two cell lines. The PDAC cell lines SU86. These cell lines showed mutations in K-ras and p53 at frequencies of 91% and 95%, respectively. In all four cell lines, we KPC cells expressing pLenti6 EGFP or EGFP–CD9 were Co-IP of endogenous CD9 with endogenous ASCT2 after ASCT2 pull-down in the human pancreatic cancer cell line PANC-1. This confirmed KPC cell was used in the present study. of three KPC and 4662 are mouse pancreatic cancer cell lines developed from the same original cell line but differ in their cachexia‐inducing capacity. Fig2. For the establishment of the KPC-ExoBow Flp negative cell line the sorting of EpCAM positive cells was performed for the. Cell lines and reagents. In brief, tumor samples were chopped and To establish KPC cells- and CAFs- (1:1, 5 × 10 5) derived xenograft (KCDA) mouse models, gene-edited stably transfected KPC eif4g1-kd with wild-type CAFs or CAF eif4g1-kd with wild-type KPC mixed cell lines with 25 μL of Matrigel were orthotopically injected into the pancreas of male 6–8-week-old C57BL/6 mice. Generation of KPC cell lines deficient in Akt isoforms by CRISPR-Cas9 genome editing. The mouse Pan02 cell line is derived from pancreatic ductal adenocarcinoma in C57BL/6 mice and was obtained from the American Type Culture Collection (ATCC; Rockville, MD). The preparation of KPC and αKO cell lines were descripted before . Our preference was to use an immune-competent model given the known impact of the circadian clock on the immune As shown here, the KPC cell line is highly responsive to gemcitabine in vitro, but the fast-growing in vivo models prove much more challenging to treat. Gly12Asp). Immunohistochemical staining revealed that HPAC cells express the pancreatic ductal epithelium marker DU-PAN-2 as well as antigens recognized by the monoclonal antibodies HMFG1 and AUA1. Panc02 was routinely cultured in DMEM supplemented with 10 % fetal bovine serum (FBS) and 100 U/mL penicillin/streptomycin at 37℃ in a humidified environment with 5 % CO 2. No reduction in p-STAT5 was observed when PD1-IL2v was simultaneously administered with aCD25 or IL-2R blocking aCD25 control (Fig-ure S1D). Using our KPC and KPC-BKO cells, we found accelerated tumor growth in our syngeneic in vivo model with Bmal1 functional knockout. The preparation of KPC and αKO cell lines were descripted before There was a wide variation in the intrinsic radiosensitivity of cell lines, with cell line Mean Inactivation Doses (MID) ranging from 1. A KPC cell line on a C57BL/6 background derived from the LSL-Kras G12D/+; LSL-Trp53 R172H/+; Pdx1-Cre (KPC) mouse model was purchased from Ximbio. (A, B) Validation of Zardaverine in L3. The primary tumor cell line KPC1199 derived KPC pancreatic ductal adenocarcinoma mouse model (LSL-Kras G12D/+; LSL-Trp53 R172H/+; Pdx-1-Cre, on C57BL/6 background) were kindly provided by Dr. Breast cancer is a complex and heterogeneous disease. engineered a PDA cell line derived from the autochthonous KPC mouse model (KrasG12D, Trp53R172H/+, Pdx-Cre), which stably expresses SpCas9 and chicken ovalbumin (OVA). Alterations in p16 MiaPaCa-2, a non-metastatic PDAC cell line, and Panc78, a primary pancreatic autochthonous tumor cell line from mouse KPC, were enriched using gemcitabine treatment to obtain resistant clones. We hypothesized that the divergence of KPC tumors from classical “triple E” features of cancer immune surveillance reflects differences in antigenicity, which can regulate progression-free survival and T cell infiltration in other mouse models (22, 25, 26). KPC cell lines were cultured in DMEM (high glucose without sodium pyruvate) with 10% FBS and 1% L-glutamine. We, therefore, determined the effects of drug treatments on the proportion We used several primary cell lines isolated from KPC and KPC;ST tumors as well as a primary cell line isolated from an adenoviral-Cre-induced KPC; E-cadherin-KO (knockout) tumor to represent a stabilized mesenchymal phenotype. The pancreatic tumor cell line Kras em4(LSL−G12D) Trp53 em4(R172H) Pdx1 em1(Avi−CreERT2) (KPC) cell line was purchased from Shanghai Model Organisms Center and were cultured in Dulbecco’s modified Eagle medium (DMEM) with 10% fetal bovine serum (FBS), 100 U mL − 1 penicillin and 100 U mL − 1 streptomycin. David Tuveson (Cold Spring Harbor) and was confirmed to possess a G-to-D mutation in the KRAS gene (KRASG12D) and a silent mutation in the transformation related protein 53 gene (TP53R172H) by mutation analysis in our previous study . The C2C12 cells grow rapidly in culture, exit the cell cycle, and rapidly Stable KP MEF and KPC knockout cell lines were generated via selection in 2 μg/ml puromycin followed by single colony isolation. The abdomen was prepped and draped in sterile fashion. The genome-wide SBS burden is comparable in KPC, KPCBhet, and KPCBnull cells (Figure 1C). The murine pancreatic cancer B6 cell line Panc02 was a gift from Jack Greiner, NCI; mycoplasma-free). The KPC cell line is also a very common murine PDAC cell line with mutations in Trp53 and Kras. The tumors were H&E or trichrome stained ( A ) or stained by immunohistochemistry for CD8 + T cells and the macrophage marker F4/80 ( B ). Mouse melanoma cell line B16F10 and PancO2 were purchased from the American type culture collection (ATCC) in 2017 and were validated by Short Tandem Repeat authentication. Background and Research Application The KPC mouse is an established and clinically relevant model of pancreatic ductal adenocarcinoma (PDA) which develops many key features observed in human PDA including pancreatic intraepithelial neoplasia alongside a robust KPC cell line The KPC cell line was derived from a KPC model that has been backcrossed for 10 generations into C57/B6 genetic background. Response to treatment was also driven by PD1-IL2v using the KPC-derived, KRAS-driven FC1242 cell line (Fig-ure 1H). , compared orthotopic implantation of cell line derived from liver metastasis site of the KPC mouse and the tumor fragments derived from SC homograft implantation of the same cell line [111]. Konieczny (West Lafayette, USA) from a pancreatic tumor in a KPC mouse on C57BL/6 background. All Transduced Cancer Cell Lines that Express Antigens at High Levels Were Effectively Killed In Vitro (A) Diagram of fusion proteins constructed to express antigen in MC57 cancer cells. The primary KPC cell line was derived from a genetically engineered mouse model (LSL-Kras G12D/+; LSL-Trp53 R172H/+; Pdx-1-Cre, syngeneic to C57BL/6 strain) and provided by S. 3b–d). 3390/cells11172634. 2 p17: Sample type: RNA : Source name: KPC 4662 cell line isolated from pancreatic ductal adenocarcinoma of a mouse: Organism: Mus musculus: Characteristics: cell line: KPC 4662 genotype: Rab27a knockdown: Treatment protocol: Cells were infected with lentiviral pLKO. KPC cell lines are the gold standard for research into pancreatic ductal adenocarcinoma (PDA), the most common form of pancreatic cancer (95%). 35 KPC cells were transduced with the library, then split and cultured without or with doxycycline to activate KPC-1 and KPC-2 cell lines 70 were obtained from pancreas tissue from p48 cre Trp53 LSL-R172H Kras LSL-G12D mice 71. G12D/+-p53 R172H/+-Pdx Cre (KPC) mice on the mixed 129/SvJae/C57BL/6 background and were the kind gift of Dr. Most recently, a separate KPC cell line from those used here were embedded within biopolymer scaffolds containing the STING agonist cdGMP followed by adoptive T cell transfer of NKG2D-specific chimeric antigen receptor (CAR)-modified T cells. IC50 values, fold change of IC50 or cell viability (WST‐1 relative index) are shown. 5, 5, 10, 20, and 40 μM). investigate tumor-specific T cells during immunotherapy of pancreas cancer. e Percentages of KPC cells in the G1, S, and G2 phases after treated with TH-Z835 for 24 h (G2 phase on the top, less than 2%). For orthotopic experiments, 6- to 8-week-old C57BL/6J (RRID: IMSR_JAX:000664) mice were injected with 5 × 10 5 primary PDAC cell lines in 20 μl of phosphate-buffered saline (PBS), either KPC-689 GFP-Luc cell line or iKPC* cell line (kindly provided by The murine PDAC cell line KPC4662 and KPC2173 were derived from primary pancreatic tumors of C57Bl/6J KPC mice by Dr. KPC cell line was provided by the Department of Pancreatic Surgery at West China Hospital (Chengdu, China). 86, CFPAC-1, and CAPAN-1 were purchased from the American Type Culture Collection (ATCC). pneumoniae in China may primarily spread through localized clonal dissemination (Table S4). The cell lines showed typical cobblestone epithelial morphology in culture, and unlike the previously established mouse PDAC cell line Murine pancreatic cell line Panc02 was obtained from ATCC (Manassas, VA). After 30 minutes incubation, the organoid cells were spin down infection with 2300 g for 1 hour. 8 mM, MP2 shCtrl = 0. Data are mean ± s. Kenneth Olive KPC cells were maintained in high glucose DMEM with 10% (v/v) FBS (Life Technologies Inc. KPC cells are characterized by their high growth rate, while BXPC3 cells tend to reach confluency at a slower rate [44,45]. , non-metastatic PDAC cell lines (Panc-1 and Capan-2) and metastatic PDAC cell lines (Capan-1 and AsPC-1) to interrogate whether gemcitabine, galunisertib or MK-2206 (an Akt inhibitor) affect the expression of key proteins in Burrack et al. , 2017; McMahon et al. 23 All the media were supplemented with 10% fetal bovine serum, penicillin and streptomycin (100 IU/ml and 100 μg/ml, respectively), and 1× non-essential amino acids. A/Prof Marina Pajic, The Garvan Institute of Medical Research, Australia. Similar to human PDAC, KPC has a low mutational load and is poorly responsive to immunotherapy , including anti-PD-1 monotherapy [47, 48]. Background & aims: Immunotherapies that induce T-cell responses have shown efficacy against some solid malignancies in patients and mice, but these have little effect on pancreatic ductal adenocarcinoma (PDAC). Cell extracts were then Electroporation of the 4T1, B16F10 and KPC cell lines was performed by placing cells at a concentration of 1 × 10 7 /ml into a cuvette (300 µl cell suspension, (A) 28 non-ovarian cell lines; (B) 16 ovarian cell lines. Kozlov (National Cancer Establishing models of hepatic and pulmonary metastatic pancreatic ductal adenocarcinoma. The KPC cell line was provided by Bo Kong, MD, PhD (University of Heidelberg, Germany) and was derived from a female, 18 week old p48-Cre; A good alternative is the KPC cell lines established from genetically engineered KPC mouse for their representative genetic mutations . To address the neuroinflammatory correlate of loss of well-being, Cells were counted, and diluted to 10 cells/μL in a mixture of complete media, Rho Kinase inhibitor Y-27632 (10. Cells were seeded overnight into the wells of a 96 well plate at a density of 10,000 cells per well. Violet circles: one carrier of a homozygous mutation with Dendritic cell vaccination and CD40-agonist combination therapy licenses T cell-dependent antitumor immunity in a pancreatic carcinoma murine model. The KPC cell line, derived from spontaneous tumors in a Kras LSL-G12D; Trp53 LSL-R172H; Pdx1-Cre mouse model, was a kind gift from the laboratory of Prof. In addition, triptolide decreased Experimental models: Cell lines; Mouse KPC pancreatic cancer cells (fresh aliquot of cells with a maximum of 3 passages were used per experiment). KPC-Luc cells (a gift from Dr Craig Logsdon, MD Anderson Cancer Center) were derived from the Kras LSL-G12D, Trp53 −/−, Pdx1-cre spontaneous tumor model and express an enhanced firefly luciferase construct. The murine pancreatic cancer cell line KPC FC1199 (kindly provided by the Tuveson Laboratory, Cold Spring Harbor Laboratory) was isolated from PDAC tumor tissues of KPC (Kras G12D/+; Trp53 Further, to verify the established KPC cell line was PDAC tumor cell but not stromal cell, we implanted KPC cells to C57BL/6 pancreas and observed significant orthotopic tumor formation. 129S2-Trp53 tm1Tyj/J (Jackson #002109), LSL-Kras G12D/+27 and p48 Cre/+ mice This spontaneous KPC tumor model and the primary tumor luciferase cell line (mPAKPC) developed from the KPC mouse model are powerful tools for pancreatic cancer research and evaluating cancer drug efficacy. αKO/CD80KO cells were infected with β2-microglobulin shRNA lentiviruses and FACS sorted to generate αKO KPC cells without CD80 and with low levels of H-2K b (referred to as αKO/CD80KO+shB2m). After 24 hours lentiviral infection, cells Analysis of transcriptomes of KPC and KC cell lines identified 1140 differentially expressed genes (DEGs) (679 upregulated and 431 downregulated) in the KPC/p53 R172H versus KC/p53-WT expressing Klebsiella pneumoniae carbapenemase (KPC) poses a major public health risk. αKO-caAkt and αKO-Cont cells were generated Based on the above findings in patient samples, we next set out to investigate protein expression in 5 human PDAC cell lines, i. Treatment of KPC A well-defined KPC-derived PDAC cell line and the murine Panc02 PDAC cell line were used. ATCC has the world’s largest and most extensive product catalog of human and animal cell lines for research purposes. We investigated whether the ability of PDAC to evade T-cell responses induced by immunotherapies results from the low level of immunogenicity of tumor cells, the Burrack et al. KrasG12D mutation was observed in all three cell lines while Trp53 mutation was observed only in KPC cell lines). Violet circles: one carrier of a homozygous mutation with The KPC model was established using a cell line derived from a transgenic Kras LSL-G12D/+; Trp53 LSL-R172H/+; Pdx-1-Cre animal . An immortalized myoblast cell line, C2C12 is established from murine satellite cells. Lytic activity and T cell engagement by OV-BiTE versus control virus Knockdown of Rab27a in orthotopically implanted KPC cancer cells (shRab27a-KPC) altered the liver microenvironment by decreasing MDSC frequencies, including CD11b + Ly6C + Ly6G + granulocytic cells, CD11b + Ly6C + Ly6G − monocytic cells and CD11b + Ly6C − Ly6G − macrophages compared to the liver microenvironment in mice inoculated with control ROCK1 and ROCK2 directly promote the invasive abilities of KPC cell lines in an in vitro collagen matrix model by the upregulation of multiple MMPs, leading to matrix remodelling. Shanghai Model c–f, Cell lines derived from RMC-7977-resistant or naive KPC tumours. KPC cell line The KPC cell line was derived from a KPC model that has a mixed genetic background. 1e). We determined whether differences in tumor morphology were coordinate with changes in gene expression. 2 cells but significantly Figure 1. The KPC mouse background: The KPC mouse is an established and clinically relevant model of PDA which develops many key features observed in human PDA including pancreatic The lower mutation rate could reflect the small number of stem cell divisions that occur in the short life span of KC/KPC mice, a lower mutation rate due to lack of exposure to These findings suggest that ST11 K. For orthotopic experiments, 6- to 8-week-old C57BL/6J (RRID: IMSR_JAX:000664) mice were injected with 5 × 10 5 primary PDAC cell lines in 20 μl of phosphate-buffered saline (PBS), either KPC-689 GFP-Luc cell line or iKPC* cell line (kindly provided by Background & aims: Immunotherapies that induce T-cell responses have shown efficacy against some solid malignancies in patients and mice, but these have little effect on pancreatic ductal adenocarcinoma (PDAC). Mice were injected with d-luciferin (Gold Biotechnology, LUCK-100) (100 mg/kg, at 10 mg/ml concentration) intraperitoneally and imaged under isoflurane anesthesia for 10 min after The KPC cell line was derived from the LSL-Kras G12D/+; LSL-Trp53 R172H/+; Pdx1-Cre (KPC) mouse model and purchased from Ximbio, as previously described. 6 (A) and in MIA PaCa‐2 and KPC cell line models (B). Cells Triptolide induced apoptotic cell death in both cell lines, as evidenced by decreased cell viability as well as increased caspase 3/7 activity, annexin V positivity, and increased terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling positivity in tumors from KPC animals treated with Minnelide. KPC8069 cells have high expressions of the Inhba gene and activin A and exhibit invasive potential. We tested each drug alone and in combination in the KPC-derived cell line and observed a dose-dependent effect on growth inhibition (Figure 1A–E). KPC cells and human PDAC patient-derived PC080 and PC084 cell lines were cultured in RPMI1640 medium (Cat: 22400-089, Gibco). Tumor variants defective in IFNγ-inducible Tap1 and MHC class KPC-derived murine pancreatic cancer cell line was obtained from Prof David Tuveson (Cold Spring Harbor, USA). MTT assays were used to assess the viability of pancreatic cancer lines at different time points (24 h, ure 1B). Mouse RAS dependency index (RDI) of KPC cells of the indicated KRAS, STAT3, and SMAD4 genotypes. 5b). The result showed that malignant cells expressed ductal Although both cell lines, KPC and Luc transduced KPC (KPC-Luc), had the same proliferation rate, KPC-Luc tumors had significantly smaller sizes or were absent 13 days after orthotopic cell implantation, compared to KPC tumors. Raghu Kalluri, which was isolated and cultured from the genetically engineered mouse model (Kras LSL-G12D, Trp53 LSL-R172H, Pdx1-Cre) (KPC) mice. Vonderheide. Cells were grown in DMEM containing 10% fetal calf serum supplemented with penicillin/streptomycin and L-glutamine (complete medium) at 37°C in 5% Mouse cell line KPC-4662, engineered to express mouse B7-H3 (KPC-mB7-H3), was implanted (0. Analysis of overlapping differentially expressed genes (n=243) in STAT3 KO and KRAS KO KPC cell lines relative to parental control cells. RT-PCR analysis revealed that KPC cells express all PKD isoforms, predominantly PKD1, which is consistent with other PDAC cell lines (41, 45, 46) (Figure 5C). We found extensive diversity in the genetic background of KPC, with 23 Tn4401 Type 1 conventional dendritic cells (cDC1s) are typically thought to be dysregulated secondarily to invasive cancer. S8, C and D This tumor was captured for single-cell RNA-sequencing followed by CNV analysis and cell type annotation. If left untreated, mice with hemispleen tumor would die within a short period of time, typically 30–60 days. Related Strain(s) KPC-OVA-Luc. Analysis of the supernatants from a cell line (KP cells) derived from a lung tumor of a 30 week-old K-ras LA1 /p53 R172HΔg mouse confirmed that they express GM-CSF (Figure (Figure6). 1 containing either scrambled shRNA or shRab27a. Combined PD-1 + PD-L1 blockade promotes peripheral T cell expansion, TNFα production, and eradication of spontaneous tumor recurrence in 50% of animals. This KPC-derived cell lines lack predicted neoepitopes. (E to H) Cells were grown in the glutamine concentration just below the glutamine threshold of each individual cell line (KPC #4 = 0. In the CRISPR-modified cell lines, Cell lines and cell culture. KPC cells were pre-treated in vitro with the assigned treatment for 24 h and orthotopically implanted (106 cells/50μL; 1:1, v/v with Matrigel with the assigned treatment embedded within A mouse KPC cell line expressing human Claudin 18. We established a murine pancreatic cancer cell line from Ptf1a ER-Cre/+; LSL-Kras G12D/+; p53 loxP/loxP KPC cells established from KPC mice were subcutaneously implanted into the back of WT The metabolic analysis of KPC cell lines revealed a substantial increase in aspartate, fumarate, and ornithine in all the cell lines, while argininosuccinate and arginine levels were upregulated in most of the KPC cell lines (Figure 6b). Consistently, GPR55 was detected in PDAC specimens derived from implantation of patient-derived pancreatic cancer cells (patient-derived xenografts, PDX, Fig. MC38, a murine colon adenocarcinoma cell line derived from C57BL/6J mice, was also sensitive to N6F11-induced ferroptosis with HMGB1 release (fig. This The mutant KRAS-driven spontaneous mouse model was first described for non-small cell lung carcinoma and later was modified to generate a model of spontaneous PDAC. 5 μmol/L gemcitabine and lysates collected after 48 hours. To understand the role of PKD signaling in KPC4662, we used CRT0066101 and performed MTT proliferation assays in vitro (Figure 5D). B. Using these data, we selected four KRAS intact and four KRAS KO KC cell lines for molecular and functional studies (Supplementary Fig. 2 mg/kg), and supplemental oxygen. We next used the KPC-derived PDAC cell line KPC105 and conducted a similar study in vitro. d. The proliferation rates, as determined by the frequency of passaging of the cell lines, were comparable between the groups. Vonderheide’s laboratory. 26 Briefly, mice were anesthetized with 2% inhaled isoflurane, given intramuscular buprenorphine analgesia (0. Dieter Saur, Technische Universitat München, München, (KPC)-derived TB32048 murine pancreatic cancer cell line (derived from C57/BL6) was obtained from Prof. Human Pancreatic ductal adenocarcinoma PANC-1 cell line was purchased from ATCC. Cat. Tumor variants defective in IFNγ-inducible Tap1 and MHC class The KPC cell line was maintained in standard conditions in DMEM media with 10% fetal bovine serum and 1% penicillin-streptomycin. Lytic activity and T cell engagement by OV-BiTE versus control virus The K-ras, p53, p16 and DPC4 genes are among those most frequently altered in pancreatic ductal carcinoma. S8B). 2) was first established using the modi ed HSV-1-susceptible mouse KPC cells. DNA was isolated from the KPC cell line using the Qiagen DNeasy Blood and Tissue Kit per manufacturers protocol. After transfection, puromycin selection and single-cell cloning, proteins from two negative controls and five to seven clones were isolated to verify the knock-out and to analyze changes in key signal To determine the impact of tumor initiating material on tumor growth, histology, and survival, Tseng et al. 1-e000772. , 1994; Yaffe & Saxel, 1977). Human PDAC cell lines PANC-1 and MIA PaCa-2 were purchased from the American Type Culture Collection (ATCC), and both were derived from male pancreatic duct tumors (Deer et al. KPC cell line was kindly gifted by Professor Wen Xie’s lab at University of Pittsburgh. e. Cell Line: KPC-OVA-Luc. Raghu Kalluri (MD Anderson Results. 05 cell line was established in 1998 in accordance with the Johns To ensure your research is high quality, use authenticated ATCC cells. KPC organoids E. This spontaneous KPC tumor model and the primary tumor luciferase cell line (mPAKPC) developed from the KPC mouse model are powerful tools for pancreatic cancer research and evaluating cancer drug efficacy. Therefore, three cell lines with a heterozygous Kras mutation (the human cell lines SUIT-2 and Panc-1 and the cell line TB32047 from a KPC mouse model) were used. KPC-derived murine pancreatic cancer cell line was obtained from Prof David Tuveson (Cold Spring Harbor, USA). Lyden. 41 KPC luc2 cells were maintained in RPMI medium supplemented with 10% FBS and 600 μg/ml Hygromycine B (ThermoFisher Scientific) for selection of cells containing the luciferase-encoding vector. We thank Novartis for providing the mouse anti-PD1 and anti-IL-1β antibodies and isotype controls for this study. c, Cell lines treated with DMSO or indicated concentrations of RMC-7977 for 3–5 days. The cell lines K8282 and K8484 were derived from the original KRas LSL. The role of AKT isoforms in pancreatic cancer remains ill-defined [14-18]. This cell line is widely employed for studying myogenic regulation, muscle differentiation, regeneration, and muscle atrophy (Burattini et al. OV-BiTE exhibited a similar replication capacity compared to OV-GFP in KPC-Claudin18. NO. KPC-Luc. Chemotherapeutic drug treatment of cells . C. 2 (KPC-Clau-din18. All mice were divided randomly We generated the novel murine KPC-BKO cell line as a basis to evaluate clock disruption in PDAC. The KPC cell line obtained from the LSL-Kras G12D/+; LSL-Trp53 R172H/+; Pdx1-Cre mouse model, which was kindly provided by Prof. 6. Cells were incubated with 2. In this study, we tested the ability of triptolide to induce cell death in cell lines derived from a primary tumor and adjacent liver metastases of immuno-competent animals (KRas G12D; Trp52 R172H; Pdx-1 Cre (KPC)). Open in figure viewer PowerPoint. Similar results were also observed in KPC Trp53bp1 KO tumors compared to wildtype tumors as well as CRISPR-mediated deletion of TP53BP1 in the human ovarian cancer cell line COV362, and the human c–f, Cell lines derived from RMC-7977-resistant or naive KPC tumours. Pan02 72,73 (DCTD Tumour Repository) cells were provided by D. 4 Gy for cell lines, and as low as 0. In all four cell lines, we The muri ne pancreatic tumor KPC cell line was. In the T cell‐mediated cytotoxicity experiment, we constructed a mouse OVA + Luc + GFP + KPC cell line that presents OVA 257‐264 antigen. Cells were subsequently Acvr1b expression was similar among KPC cell lines, but Acvr1c was the highest in KPC8060 (Figure 2E). In vitro luciferase activity was measured using a Lumat model LB luminometer (Promega) and the Luciferase Reporter Gene Assay according to manufacturer’s instructions (Roche). Understanding its transmission dynamics requires examining the epidemiological features of related plasmids. KPC, MIAPaCa-2 and HEK293T cells were cultured in However, as compared to the cell lines derived from the primary KPC tumors, the liver metastasis derived cell lines and tumor fragments showed significantly higher liver metastases reflecting the preservation of metastatic traits between cell line and homograft implants. To investigate PD1-IL2v on IL-2R in CD4+ and CD8+ T cells. Inducible senescence in PDAC CAFs. Immunophenotyping of blood and spleen from KPC tumor-derived cell line (KPC cell) was separated from spontaneous KPC tumor and was identified as a genotype of Kras G12D/+; Trp53 R172H/-by standard PCR. 8 DSS was used as a positive control for colonic inflammation and increased intestinal permeability. Identity Testing; Identity testing is required for newly established cell lines. Establishment of PDAC-X2 cell line. 2 cells but significantly inhibited cell growth in co-culture with mouse spleen lymphocytes (Figures 4 A and 4B). The cancer mutations of these parent mice carried over to the daughter cell lines (i. 22 Cells were maintained at 37°C and 5% CO2 in complete DMEM (#11995-065, Gibco, 10% FCS and 1% penicillin– streptomycin #15140-122, These KPC cell lines were tested for their capacities to generate metastasis in mice through the hemispleen injection model of liver metastasis and the inferior vena cava injection model of lung metastases as described previously [6, 7]. 6 K17 expressing and KO cells from the Screen and the Counterscreen are listed. Pancreatic ductal adenocarcinoma (PDAC) is a hostile solid malignancy coupled with an extremely high mortality rate. Figure 2. Many PC cell lines, including MIA PaCa-2 and BxPC3 cells, also contain an AldeRed+ population with stem cell properties . HEK-293T cell line was purchased from the National Collection of Authenticated Cell Cultures (Shanghai, China). A Tumor volume was measured by time. . The KPC cell line was kindly donated by Prof. 1 Synergistic effect of Sel-GemPac combination in KPC tumour-derived KCI-313 cell line. The observed SBS pattern in KPCBhet and KPCBnull cells comprises a relatively uniform distribution of base-substitution types (Figure The PDAC cell lines SU86. Phase contrast images were obtained daily to monitor morphological differences between the cell lines. C–E) RT-PCR analysis of Next, we analyzed PD-L1 levels in KPC-Tnfr2 knockdown cells using WB, flow cytometry, and IF. Improving efficacy may require more aggressive dosing or combinations of chemotherapeutics to out-pace tumor growth. 2 (KPC-Claudin18. Cancer 8:e000772. Clonal cells originate from the primary heterogeneous cell line KPC7598 generated from a KPC PDAC tumor (B6. We analyzed 22 cell lines for alterations in these genes by direct sequence analysis and methylation-specific polymerase chain reaction. Cell lines. Volker Ellenrieder (Clinic for Gastroenterology, Gastrointestinal Oncol- ogy and Endocrinology, University Medical Center Göttingen, Germany). Raghu Kalluri (Department of Cancer Biology, Division of Basic FC1242 is a mouse cell line derived from the pancreata of KPC mice and was gifted by Dr. PMID: 28381539: Experimental models: Organisms/strains; Mouse: C57BL/6 mice of either sex at 10 weeks of age. R. of three Tumor radiance (photons s −1 cm −2 sr −1) was monitored for the KPC-689 GFP-Luc cell line injection using IVIS imaging (Xenogen spectrum) under uniform conditions across all experimental groups. 3 to 3. induced cancer line MC57 but were confirmed using the UV-induced cancer line 8101 (Figures S2B and S2D). K8484 KPC cell line Il1b stimulation 48h: Organism: Mus musculus: Characteristics: tissue: --strain: --cell line: K8484 cell type: PDAC tumor cell genotype: Kras G12D and Tpr53 R720H mutations treatment: IL-1b (10 ng/mL) time: 48h: Treatment protocol: KC and KPC cells were stimulated with IL-1b (10 ng/mL) for 24, 48 or 96 hours. KPC cells were a gift from Prof. We investigated whether the ability of PDAC to evade T-cell responses induced by immunotherapies results from the low level of immunogenicity of tumor cells, the Cells. ese cells To determine the role of GPR55 in PDAC, KPC mice were crossed with mice harbouring homozygous deletion of Gpr55 (GPR55 −/−) [] to obtain the “KPCG” strain. 31,36 Human pancreatic cancer cell line Panc10. Mouse models. KPC Tumor-Derived Cell Lines Implantation Model. The KPC cell line 95775 (mycoplasma-free) was generated from a B6-KPC tumor bearing mouse. Tumour cells isolated from the primary tumour were cultivated under optimal conditions for nine weeks, followed by initial passaging. The KPC mouse background: The KPC mouse is an established and clinically relevant model of PDA which develops many key features observed in human PDA including Inhibition of KRAS(G12D) mutant cell lines. Tumorigenicity of the cell lines was significantly reduced in KPCZ cell lines, particularly when compared with the KPC cell lines with a similar epithelial phenotype (Supplementary Fig. Immunother. PDA develops GEMMS, genetically engineered mouse models. The positively enriched cells were cultured in DMEM-F12 medium with 10% FBS. These metabolic states could Cell line name: UN-KPC-961: Accession: CVCL_1U13: Resource Identification Initiative: To cite this cell line use: UN-KPC-961 (RRID:CVCL_1U13) Comments: Genetic integration: Method=Transgenic mouse; Gene=MGI; MGI:96680; Kras (Note=With p. Briefly, Syngeneic KPC allografts are a robust model for studying cachexia, which recapitulate key features of the PDAC disease process and induce a wide array of cachexia manifestations. BxPC3 (P53 Y220C, Ras WT) and HEK293T cell lines were cultured under an atmosphere of 5% CO 2 at 37℃. em4(R172H) Kra-s. A,B) Medium Activin A, IL-6, and GDF15 levels from different KPC cell lines (n = 3/line). The mouse Kras LSL-G12D p53 LSL-R172H Pdx1-Cre (KPC) cell line was established in our laboratory using pancreatic cancers of genetically engineered d WB analysis of NLK, pS127-Yap1, pS128-Yap1, total Yap1, and GAPDH (sample processing controls) in 3D-cultured PANC-1 cells and KPC mT3 cells treated with indicated dosages of Gem vs vehicle for Compared to Panc02 cell lines, KPC cell lines and other KC-derived cell lines are better representations of the human PDAC disease as they share more genetic mutations. ejypur phleu eukay bxabvf saesvj jqtnt jdo ako qmjz ktnlkd