Transition to pancreatic cancer in response to carcinogen.

BACKGROUND

It has become obvious that the traditional assumptions about the transition from normal pancreas to pancreatic cancer are incomplete. Experimental studies reveal that the earliest changes during transition to pancreatic adenocarcinoma involve premalignant lesions that are derived from acinar, islet, and ductal cells.

OBSERVATIONS

Changes are rapid, occurring in days. As part of redifferentiation and transformation to adenocarcinoma, cells regain the characteristics of developing pancreas. Elements significant in identifying precursor cell types include Pdx1, hedgehog signaling, notch signaling, and nestin, an intermediate filament expressed by precursor cell types.

CONCLUSIONS

Thus pancreatic carcinogenesis is not simply a matter of transition of ductal cells to cancer cells months after insult by the carcinogen; ductal cells are not the sole source transitioning to cancer, and PanINs are not the sole route to adenocarcinoma. Tubular complexes, derived from multiple cell sources, are included in routes to pancreatic cancer. Markers characteristic of developing pancreas are consistent with this transition. Cells previously thought to be terminally differentiated become, in effect, stem cells.