Differential inhibition of renal cancer cell invasion mediated by fibronectin, collagen IV and laminin

Invasion of tumor cells into the extracellular matrix is an essential step in the formation of metastases in renal cancer. Cell adhesion molecules suc h as beta (1)-integrins, which bind to the RGD sequence (arginine-glycine-a sparagine) and CD44 are involved in this process. We examined the invasion of a renal carcinoma cell line (CCF-RC1) into the extracellular matrix comp ounds fibronectin. collagen IV and laminin and the effect of TGF beta and I FN gamma on this process. The inhibitory effect of an antibody against the beta (1)-subunit of integrins (CD29), as well as a pentapeptide including t he RGD sequence, was also evaluated. A micro-chemotaxis chamber, including a polycarbonate membrane with a pore diameter of 8 mum, was used for quanti fication of cell migration. The addition of the extracellular matrix compou nds fibronectin, laminin and collagen IV resulted in a 5-10-fold increase i n invasion. This increased invasion depends strongly on the presence of bet a (1)-integrins, shown by the use of an antibody against CD29 or a RGD incl uding peptide which inhibit the cell migration by approximately 88%. CD44 i s less involved in collagen IV dependent migration and almost no influence of CD44 was observed on a fibronectin and laminin dependent migration. TNF alpha and IFN gamma did not significantly influence the expression of CD29 or CD44, and no alteration in tumor cell migration was observed. These resu lts show that the invasion of renal cancer cells is differentially regulate d by compounds of the extracellular matrix, whereby fibronectin seems to be the most critical factor. The molecular interactions in this process are s trongly dependent on beta (1)-integrins and the corresponding amino acid se quence ROD. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.