Regulation of human colon‐carcinoma cell adhesion to extracellular matrix by transforming growth factor β1

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Abstract
The regulatory effect of transforming growth factor β1 (TGF-β1) on the adhesion of human colon-carcinoma cells to the extracellular matrix (ECM) was investigated. ECMs used in this study included tissue-culture wells coated with fibronectin, laminin, collagen and BSA, as well as plastic wells. Three phenotypically different human colon-carcinoma cell lines (Moser, HCT116, and KM 12SM) were used. The Moser cell line is moderately differentiated and, in terms of the diversity of responses elicited by TGF-β1, is the human colon-carcinoma cell line most responsive to TCP-β1 as reported to date. By comparison, the undifferentiated HCT116 and the highly meta- static KM 12SM cells are unresponsive to this growth factor. We showed that TGF-β1 regulated the adhesion responses of all 3 cell lines. However, the response profiles as well as the endogenous adhesive properties of each cell line were quite different from those of the others. Endogenous Arg-Gly-Asp(RGD)-related receptors were present on the HCT 116 but not on the other cells. The observed regulatory effect of TGF-β1 was contingent on the cell line, the type of ECM, and the growth-factor treatment protocol used. When cells were treated with TGF-PI for 16 hr prior to exposure to ECM in a 4-hr adhesion assay, a significant increase in adhesion to fibronectin and collagen was observed for the Moser cells. For the identical experimental protocol, the KM 12SM cells responded by increas- ing adhesion to fibronectin, while the HCT 116 cells responded by decreasing adhesion to collagen. Kinetic analyses of TGF-p I treatment showed that increased adhesion response to laminin was induced in the Moser cells after 2 hr of growth-factor treatment. This response declined rapidly upon further exposure of the cells to TGF-β1. Simultaneous exposure of cells to both TGF-β1 and ECM negated the adhesion responses described above. The up-modulation of adhesion to fibronectin, laminin and collagen by TGF-β1 was mediated through RGD-related integrin receptors. RGD-containing peptides effectively blocked the enhanced adhesion responses induced by TGF-β1.