46.pdf - Google Drive
Additionally, a recent study (12) has associated lineage dedifferentiation with malignant progression from pancreatic islet cell neoplasias into metastasis-prone carcinomas; these neuroendocrine cells and derivative tumors arise from a developmental lineage that is distinct from the one generating the far larger number of adjacent cells that form the exocrine and pancreas and the ductal adenocarcinomas that arise therefrom. Notably, the multistep differentiation pathway of islet progenitor cells into mature β cells has been thoroughly characterized (13). Comparative transcriptome profiling reveals that adenoma-like islet tumors are most similar to immature but differentiated insulin-producing β cells, whereas the invasive carcinomas are most similar to embryonic islet cell precursors. The progression toward poorly differentiated carcinomas involves a first step of dedifferentiation that does not initially involve increased proliferation or reduced apoptosis when compared with the well-differentiated adenomas, both of which rather occur later. Thus, the discrete step of dedifferentiation…