WES pancreatic ductal adenocarinoma cell lines

The prognosis of pancreatic ductal adenocarcinoma (PDAC) is exceedingly poor. Although surgical resection is the only curative treatment option, multimodal treatment is of utmost importance as only about 20% of tumors are primarily resectable at time of diagnosis. The choice of chemotherapeutic treatment regimens involving gemcitabine and FOLFIRINOX is currently solely based on the patient's performance status but, ideally, should be based on the tumors' individual biology. We established two novel patient-derived primary cell lines from surgical PDAC specimens. LuePanc-1 and LuePanc-2 were derived from a pT3,pN1,G2 and a pT3,pN2,G3 tumor, respectively, and clinical follow-up was fully annotated. STR-genotyping revealed a unique profile for both cell lines. The population doubling time of LüPanc-2 was substantially longer than that of LuePanc-1 (84 vs. 44 hours). Both cell lines exhibited a typical epithelial morphology and expressed moderate levels of CK7 and E-cadherin, while only LuePanc-1 also expressed vimentin, suggesting a mixed epithelial-mesenchymal differentiation of LuePanc-1. In TP53 LuePanc-1 had a missense mutation (p.R282W) and LuePanc-2 a frameshift deletion (p.P89X). BRCA2 was non-sense-mutated (p.Q780*) and CREBBP was missense mutated (p.P279R) in LuePanc-1. CDKN2A was missense mutated (p.H83Y) in LuePanc-2. Of note, only LüPanc-2 harbored a partial or complete deletion of DPC4. LuePanc-1 cells exhibited high migratory activity in real-time cell migration assays, while LuePanc-2 was refractory here. Both LuePanc-1 and LuePanc-2 cells responded to treatment with transforming growth factor-beta1 (TGF-beta1) with activation of SMAD2, however, only LuePanc-1 cells were able to induce TGF-beta1 target genes consistent with the absence of DPC4 in LuePanc-2 cells. In cell viability assays, LuePanc-1 cells were more sensitive than LüPanc-2 cells to treatment with gemcitabine and FOLFIRINOX. In summary, both patient-derived cell lines show distinct molecular phenotypes reflecting their individual tumor biology with a unique clinical annotation of the respective patients. These preclinical ex vivo models can be further explored for potential new treatment strategies and might help to develop personalized (targeted) therapy regimens.