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

Subhas Chakrabarty, Yih Jan, Michael G. Brattain, Andrew Tobon, James Varani

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51 Scopus citations

Abstract

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-β (TGF-β) (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-β (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-β 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-β 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-β had no effects on fibronectin/laminin synthesis nor on the cellular morphology of the resistant MOSER R2 cells. TGF-β 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-β 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-β in the two cell lines were not due to differences in TGF-β binding or other receptor parameters such as the expression of distinct TGF-β receptor subspecies.

Original languageEnglish (US)
Pages (from-to)2112-2117
Number of pages6
JournalCancer Research
Volume49
Issue number8
StatePublished - Apr 1989

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Chakrabarty, S., Jan, Y., Brattain, M. G., Tobon, A., & Varani, J. (1989). Diverse cellular responses elicited from human colon carcinoma cells by transforming growth factor-β. Cancer Research, 49(8), 2112-2117.