Article
Characterisation of novel ductal pancreatic adenocarcinoma cell lines in vitro as well as in diabetic mice
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Published: | April 26, 2013 |
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Introduction The incidence of pancreatic ductal adenocarcinoma (PDA) is nearly equal to mortality with a 5-year survival rate of only 5 %. Diabetes type II is a well known risk factor for the development of PDA. However, little information exists if this risk factor only increases the rate of tumor initiation and tumor promotion or can also influence the pathophysiology of fully established PDA.
Material and methods: The proliferative capacity of three novel murine ductal pancreatic adenocarcinoma cell lines (6606 PDA, 6606 Liver, 7265 PDA) was characterised by WST-assays and BrdU incorporation in vitro. In vivo we injected 2,5x105 cancer cells into the head of the pancreas in B6.V-Lepob/ob mice with manifested diabetes 2 like symptoms and lean littermates.
Results: WST Assays revealed that the 6606 PDA cell line has the highest proliferation rate (1.64±0.18; n=6) when ompared to 6606 liver (1.1±0.23; n=6) and the 7265 PDA cell line (0.81±0.11 absorbance at 440 nm; n=6). All three cell lines are gemcitabin sensitive. However, a significantly lower IC50 value of gemcitabin was observed using 7265PDA cells (0.011±0.005 µM) compared to 6606PDA (0.032±0.014 µM) and 6606liver cells (0.033±0.013 µM). In vivo experiments suggest that the orthotopic injection of these cells reproducibly generates tumors with the typical morphology of ductal pancreatic adenocarcinoma in B6.V-Lepob/ob as well as in lean littermates.
Conclusion: We characterized novel PDA tumor cell lines in vitro and established a syngeneic orthotopic tumor model to study the influence of type II diabetes on tumor growth and tumor stroma interaction.