Differential sensitivity of subclasses of human colon carcinoma cell lines to the growth inhibitory effects of transforming growth factor-β1

Naseema M. Hoosein, Mary K. McKnight, Alan E. Levine, Kathleen M. Mulder, Karla E. Childress, Diane E. Brattain, Michael G. Brattain

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Abstract

In this study we have employed a model system comprising three groups of colon carcinoma cell lines to examine the growth-inhibitory effects of two molecular forms of transforming growth factor-β (TGF-β), TGF-β1 and TGF-β2. Aggressive, poorly differentiated colon carcinoma cells of group I did not respond to growth inhibitory effects of TGF-β1 or TGF-β2, while less aggressive, well-differentiated cells of group III displayed marked sensitivity to both TGF-β1 and TGF-β2 in monolayer culture as well as in soft agarose. One moderately well-differentiated cell line from group II which has intermediate growth characteristics failed to respond to TGF-β1 or TGF-β2, but the growth of two other cell lines in this group was inhibited. TGF-β1 and TGF-β2 were equally potent, 50% growth inhibition for responsive cell lines being observed at a concentration of 1 ng/ml (40 pM). Antiproliferative effects of TGF-β1 and TGF-β2 in responsive cell lines of groups II and III were associated with morphological alterations and enhanced, concentration-dependent secretion of carcinoembryonic antigen. Radiolabeled TGF-β1 bound to all three groups of colon carcinoma cells with high affinity (Kd between 42 and 64 pM). These data indicate for the first time a strong correlation between the degree of differentiation of colon carcinoma cell lines and sensitivity to the antiproliferative and differentiation-promoting effects of TGF-β1 and TGF-β2.

Original languageEnglish (US)
Pages (from-to)442-453
Number of pages12
JournalExperimental Cell Research
Volume181
Issue number2
DOIs
StatePublished - Apr 1989

ASJC Scopus subject areas

  • Cell Biology

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    Hoosein, N. M., McKnight, M. K., Levine, A. E., Mulder, K. M., Childress, K. E., Brattain, D. E., & Brattain, M. G. (1989). Differential sensitivity of subclasses of human colon carcinoma cell lines to the growth inhibitory effects of transforming growth factor-β1. Experimental Cell Research, 181(2), 442-453. https://doi.org/10.1016/0014-4827(89)90101-8