Background: Most pancreatic ductal adenocarcinoma (PDAC) patients who undergo tumor resection will develop postoperative liver metastasis within the first 2 years. Our hypothesis was that, during liver colonization, the temporal modulation of processes related to metastasis will change in a specific manner and that information on these changes might be used for new therapeutic approaches.
Material and methods: PDAC rat ASML cells were inoculated into the liver of BDX rats and re-isolated after different time periods of liver colonization (early, intermediate, advanced, and terminal). The total RNA of these samples was used to evaluate the expression profiles of more than 23,000 genes by chip array analysis.
Results: Depending on the time span following re-isolation, 7-15% of all known genes were deregulated. These genes were assigned to metastasis-related processes during the 4 stages of colonization. Except for apoptosis, all other processes were not activated in the early and middle colonization stages. In the terminal phase of liver colonization, cell proliferation, cell homing, cell movement, and vasculogenesis were significantly activated.
Conclusion: We hypothesize that targeting the relatively few deregulated genes in the early stage of liver colonization could ultimately improve the survival of PDAC patients.
© 2014 S. Karger GmbH, Freiburg.