Progastrin Peptides Increase the Risk of Developing Colonic Tumors: Impact on Colonic Stem Cells

Pre-neoplastic lesions (ACF, aberrant-crypt-foci; Hp, hyperplastic/dysplastic polyps) are believed to be precursors of sporadic colorectal-tumors (Ad, adenomas; AdCA, adenocarcinomas). ACF/Hp likely originate due to abnormal growth of colonic-crypts in response to aberrant queues in the microenvironment of colonic-crypts. Thus identifying factors which regulate homeostatic vs aberrant proliferation/apoptosis of colonocytes, especially stem/progenitor cells, may lead to effective preventative/treatment strategies. Based on this philosophy, role of growth-factors/peptide-hormones, potentially available in the circulation/microenvironment of colonic-crypts is being examined extensively. Since the time gastrins were discovered as trophic (growth) factors for gastrointestinal-cells, the effect of gastrins on the growth of normal/cancer cells has been investigated, leading to many discoveries. Seminal discoveries made in the area of gastrins and colon-cancer, as it relates to molecular pathways associated with formation of colonic tumors will be reviewed, and possible impact on diagnostic/preventative/treatment strategies will be discussed.