Primary pancreatic ductal adenocarcinoma cell cultures represent the features of native tumours
Keywords: pancreatic cancer, patient’s primary cell culture, platelet-derived growth factor receptor, neoplasm drug resistance
AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer due to the lack of diagnostic tools at the early stage and low efficiency of current chemotherapeutic approaches. The anticancer compounds with proven efficiency in established cell cultures often fail validation in further research. In this study, we employed PDAC patient-derived primary cell cultures to evaluate the efficiency of chemotherapeutic agents. Alongside, patients’ tissue samples were analysed by high-throughput differential proteomic analysis. We have shown that main firstline chemotherapeutic agents gemcitabine and FOLFIRINOX have little to no effect on the viability of patient-derived primary PDAC cells. The comparative proteomic and bioinformatic analysis of PDAC tumours shows an increase in the components of the extracellular matrix and focal adhesions and also overexpression of the downstream signaling from a variety of receptors, most notably PDGF receptor β and ErbB1 receptor. Consistently, all tumour-derived cell cultures assayed express a high level of PDGF receptor β. The enhancement of multiple signaling pathways leads to the increase in cell survival, proliferation, and resistance to apoptosis. Here we demonstrated the promising value of patient-derived primary PDAC cultures as a model for anticancer drug research and evaluation for individualized therapy.