Diverse cellular responses elicited from human colon carcinoma cells by transforming growth factor-beta

We have recently characterized the growth-inhibitory and cellular responses [carcinoembryonic antigen (CEA) secretion, protein secretion, protein expression, fibronectin and laminin synthesis] of the human colon carcinoma MOSER cell line to transforming growth factor-beta (TGF-beta) (Cancer Res., 47: 2950, 1987; 48: 4059, 1988). We have also recently isolated a subline (MOSER R2) from the parental MOSER cells which, unlike the parental line, is relatively resistant to the growth-inhibitory effect of TGF-beta (Biochem. Biophys. Res. Commun., 150: 711, 1988). We now report on the characterization of the cellular responses of this resistant MOSER R2 subline to TGF-beta and compare its responses to that of the highly growth-inhibition-sensitive MOSER cell line. In view of the reported relationship between CEA expression and differentiation in colon cancer and the ability of colon-derived substrata material to modulate the phenotypic properties of colon cancer cells, additional characterization and direct comparison of the effects of TGF-beta on the two cell lines were also performed with respect to (a) cellular expression of CEA and CEA cross-reactive glycoproteins; and (b) colon-derived substrata material. Unlike the growth-inhibition-sensitive MOSER cells, TGF-beta had no effects on fibronectin/laminin synthesis nor on the cellular morphology of the resistant MOSER R2 cells. TGF-beta was also unable to modulate protein secretion and deposition of substrata material by these cells. However, several other responses of the resistant cells to TGF-beta were found to be similar to that of the sensitive MOSER cells. These responses include: (a) a prolonged and stable secretion of CEA; (b) a prolonged and stable induction of elevated cellular expression of CEA and CEA cross-reactive glycoproteins; and (c) enhancement of the expression of three cellular proteins with molecular weights corresponding to 52,000, 48,000, and 42,000. We further report that the differences observed in the responses to TGF-beta in the two cell lines were not due to differences in TGF-beta binding or other receptor parameters such as the expression of distinct TGF-beta receptor subspecies.