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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

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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)-1β, tumor necrosis factor (TNF)α and interferon γ]. 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 β 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-1β and TNFα were always undetectable. In conclusion, a clear correlation between structural/genetic features and function could not be detected, suggesting the weakness of a “morphological” classification for the in vitro studies of pancreatic cancer.

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Acknowledgements

This work was supported by grants from the Ministry of Universities and Research (MURST) (Cofin. 2002) and Italian Association for Cancer Research (AIRC).

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Authors and Affiliations

  1. Laboratory of Experimental Surgery, Department of Diabetes and Transplant Immunology, S. Raffaele Scientific Institute, Via Olgettina 60, 20132 , Milan, Italy

    Paolo Monti, Alessia Mercalli, Valeria Sordi, Alessandro Zerbi, Giampaolo Balzano, Valerio Di Carlo & Lorenzo Piemonti

  2. Department Immunology and Cell Biology “Mario Negri” Institute, Via Eritrea 62, 20157 , Milan, Italy

    Federica Marchesi & Paola Allavena

  3. Department of Oncology, S. Raffaele Scientific Institute, Milan, Italy

    Michele Reni

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  1. Paolo Monti
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  2. Federica Marchesi
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Correspondence to Lorenzo Piemonti.

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Monti, P., Marchesi, F., Reni, M. et al. A comprehensive in vitro characterization of pancreatic ductal carcinoma cell line biological behavior and its correlation with the structural and genetic profile. Virchows Arch 445, 236–247 (2004). https://doi.org/10.1007/s00428-004-1053-x

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