Integrin-receptor-mediated differentiation and growth inhibition are enhanced by transforming growth factor-beta 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-beta s (TGF-beta s) 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-I 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-beta s 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-beta s was partially inhibited by an Arg-Gly-Asp (RGD)-containing peptide which is a cell recognition signal for collagen binding. This suggests that TGF-beta s 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-beta s. This suggests that cell responsiveness to TGF-beta s may depend, at least in part, upon the cell-matrix interaction.
Pignatelli
M
M
Director's Laboratory, Imperial Cancer Research Fund, London, UK.
Bodmer
W F
WF
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000473:pathology*; D006801:Humans; D016023:Integrins; D008562:Membrane Glycoproteins / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D038981:Receptors, Collagen; D015291:Transforming Growth Factors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016023:Integrins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D038981:Receptors, Collagen; D015291:Transforming Growth Factors; D003094:Collagen