Investigation the Ability to Produce Induced Pluripotent Cells from Human Pancreatic Cancer Xenografts

There is increasing evidence that cancer cells in addition to multiple genetic mutations, also acquire epigenetic abnormalities during development, maintenance, and progression. By utilizing the reprogramming technology as a tool to introduce the ‘pressure’ to alter epigenetic regulations, we might be able to clarify the epigenetic behavior that is unique to cancer cells. So far, iPSCs have been generated from normal primary cells, but it is unclear whether human primary cancer cell can be reprogrammed. We investigated the production of the iPS cells from the pancreatic adenocarcinoma cells using defined transcription factors. We sought to reprogram patient derived xenograft from human PDAC, by introducing lentiviral mediated induction of Yamanaka Factors (OSKM) and characterized of induced cells by Alkaline Phosphatase staining, Real-Time PCR and immunostaining.  This study with research ethics code EC/93/1025 has been approved by research ethics committee at Royan Institute. Alkaline Phosphatase staining, Real-Time PCR and immunostaining showed that induction with the OSKM results in generating iPS cell line from fibroblast cells but not from PDAC PDX cells .We showed that, PDAC cells could not fully reprogrammed by the expression of 4 transcription factors. This study demonstrated that the PDAC-PDX cancer cells were distinct from PDAC induced cells with regard to their epigenetic modifier genes expression pattern, although the expression of pluripotency genes did not increased significantly in the induced PDAC cells.