Integrin‐receptor‐mediated differentiation and growth inhibition are enhanced by transforming growth factor‐β in colorectal tumour cells grown in collagen gel

We have studied the role of cell‐matrix interactions and the modulating effect on these of transforming growth factor‐βs (TGF‐βs) in controlling differentiation and proliferation in a series of human colorectal carcinoma cell lines. Two (SW1222 and SW480) out of 7 cell lines specifically bound type‐1 collagen, via integrin‐like (SW1222) and non‐integrin‐like (SW480) collagen receptors. Binding of these receptors may be responsible for regulating the degree of epithelial differentiation of the cells when grown in a 3‐dimensional (3D) collagen gel. We have also shown that TGF‐βs enhance the binding of SW1222 cells to collagen and that this is accompanied by greatly increased crypt‐like glandular differentiation and inhibition of cell proliferation. Inhibition of cell proliferation was only seen when cells were grown in 3D collagen gel and were thus expressing a fully differentiated phenotype. The enhanced collagen binding induced by TGF‐βs was partially inhibited by an Arg‐Gly‐Asp (RGD)‐containing peptide which is a cell recognition signal for collagen binding. This suggests that TGF‐βs mediate their effects on differentiation of SW1222 cells specifically by modulating the expression of the integrin‐like collagen receptor. The other colorectal carcinoma cell lines which lack this integrin‐like receptor either failed to bind collagen or, in the case of SW480 binding, exhibited differentiation and proliferation which were not affected by TGF‐βs. This suggests that cell responsiveness to TGF‐βs may depend, at least in part, upon the cell‐matrix interaction.