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A comprehensive in vitro characterization of pancreatic ductal carcinoma cell line biological behavior and its correlation with the structural and genetic profile
Authors:Paolo?Monti  Federica?Marchesi  Michele?Reni  Alessia?Mercalli  Valeria?Sordi  Alessandro?Zerbi  Giampaolo?Balzano  Valerio?Di?Carlo  Paola?Allavena  Email author" target="_blank">Lorenzo?PiemontiEmail author
Institution:(1) Laboratory of Experimental Surgery, Department of Diabetes and Transplant Immunology, S. Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy;(2) Department Immunology and Cell Biology ldquoMario Negrirdquo Institute, Via Eritrea 62, 20157 Milan, Italy;(3) Department of Oncology, S. Raffaele Scientific Institute, Milan, Italy
Abstract:There are a large number of stable pancreatic ductal carcinoma cell lines (PDCL) that are used by researchers worldwide. Detailed data about their differentiation status and genetic alterations are present in the literature, but a systematic correlation with cell biological behavior is often lacking. PDCL (n=12) were clustered by source of tumor cell (ascites, primary tumor, metastasis), and the data of functional cell biology were correlated with the reported structural and genetic profiles. Major histocompatibility complex expression, chemosensitivity and aneuploidia appeared to be related to the source of PDCL, and proliferative capacity appeared to be related to the grade of differentiation. No correlation between genetic/structural features of PDCL and biological behavior was found. All the cell lines appeared generally insensitive to in vitro treatment with 5-fluorouracil and showed variable degrees of susceptibility to gemcitabine, raltitrexed and oxaliplatin. All the PDCL showed resistance to Fas-mediated apoptosis but were significantly sensitive to the pro-apoptotic effect of inflammatory cytokines interleukin (IL)-1beta, tumor necrosis factor (TNF)agr and interferon gamma]. PDCL were characterized for the secretion of several factors relevant to the tumor-immune cross talk. Vascular endothelial growth factor, CCL2, CCL5 and transforming growth factor beta were the factors most frequently released; less frequent was the secretion of CXCL8, CCL22, IL-6 and sporadically CXCL12, IL-10 and hepatocyte growth factor. The cytokines IL-1beta and TNFagr were always undetectable. In conclusion, a clear correlation between structural/genetic features and function could not be detected, suggesting the weakness of a ldquomorphologicalrdquo classification for the in vitro studies of pancreatic cancer.
Keywords:Pancreatic cancer  Cell lines  Chemo-sensitivity  Immunoescape  Apoptosis
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