REGULATION OF FIBRONECTIN AND LAMININ RECEPTOR EXPRESSION, FIBRONECTIN AND LAMININ SECRETION IN HUMAN COLON-CANCER CELLS BY TRANSFORMING GROWTH FACTOR-BETA(1)

Transforming growth factor (TGF)-beta(1) modulates the expression of e xtracellular matrix (ECM) glycoproteins, fibronectin and laminin and t he adhesion of Moser colon cancer cells to these glycoproteins. Since adhesion can be altered through expression of cell-surface receptors, binding affinities of adhesion molecules for receptors, or both, we in vestigated the effect of TGF-beta(1) on the binding properties of fibr onectin and laminin to their cell-surface receptors by saturations bin ding and Scatchard analyses using radiolabeled fibronectin and laminin . Fibronectin bound to its cell-surface receptor with high affinity (K -d = 1.25 x 10(-9) M), Moser cells had approximately 7.1 x 10(4) fibro nectin-binding sites per cell. TGF-beta(1) treatment rapidly up-modula ted the number of cell-surface fibronectin-binding sites by 1.9-fold. The binding affinity of fibronectin for the receptor, however, was not altered. Laminin was found to bind to a higher-affinity and a lower-a ffinity receptor. Moser cells expressed approximately 1.1 x 10(3) high er-affinity laminin-bindingsites and approximately 3.1 x 10(4) lower-a ffinity-binding sites per cell. TGF-beta(1) rapidly increased the expr ession of the higher-affinity of both the higher-affinity and lower-af finity laminin receptors increased 3-fold after 2 and 6 hr of TGF-beta (1) treatment respectively. Concurrent with receptor modulation, TGF-b eta 1 induced the secretion of fibronectin and laminin from Moser cell s. Northern hybridization analyses showed a concurrent stimulation of the expression of the mRNAs for ligands (fibronectin and laminin) and the mRNAs for the integrin species of the fibronectin and laminin rece ptors (alpha 5 and alpha 6 subunits). Thus the production of fibronect in and laminin and the expression of their receptors were tightly co-r egulated by TGF-beta(1). (C) 1994 Wiley-Liss, Inc.