Transforming growth factor-beta in intestinal epithelial differentiation and neoplasia (review)

Transforming growth factor beta (TGF-beta is a multifunctional regulator of cell growth. It has become increasingly clear that TGF-beta action depends on the responsive cell types. Thus TGF-beta stimulates proliferation of mesenchymal cells and, in contrast, inhibits the growth of a large variety of epithelial cells. Recent studies, albeit controversial, support the notion that a gradient in mRNA transcripts encoding TGF-beta is maintained along the crypt-villus continuum of the small intestine in close correlation with the stage of differentiation of the enterocyte. Exogenous TGF-beta has been shown to inhibit the proliferation of a non-transformed rat jejunal crypt cell line. Additional salient findings have indicated that colon carcinoma cell lines recalcitrant to the restraining action of TGF-beta on proliferation are poorly differentiated, and that moderately differentiated colon tumor lines do retain, at least partly, their responsiveness to TGF-beta. To the best of our knowledge, no evidence is available pertaining to a contributory role of TGF-beta in the signalling mechanisms regulating growth and differentiation of normal colonic epithelial cells. In addition, we are ignorant of whether the interesting findings related to a functional relationship between TGF-beta and colon carcinoma cells lines (vide supra) are applicable to colonic preneoplastic and tumor cells in their natural habitat. In this review, we dwell on the available facts and missing observations, and present conceivable hypotheses pertaining to a putative role of TGF-beta in colon differentiation and neoplasia.