INTEGRIN EXPRESSION ON CELL-ADHESION FUNCTION AND UP-REGULATION OF P125(FAK) AND PAXILLIN IN METASTATIC RENAL-CARCINOMA CELLS

Integrins from normal human renal cortex epithelial cells (RCEC) and f rom four renal carcinoma lines (metastatic Caki-1, non-metastatic Caki -2, metastatic ACHN, and nonmetastatic 769-P) were compared by immunop recipitation with specific anti-integrin antibodies. Integrin alpha(2) was present in normal RCEC, but absent in all four tumor lines. There was a 2.0-3.0 fold decrease of alpha(3) and beta(1) in localized tumo r lines, and a further 5.0-7.0 fold decrease in metastatic lines over their expression in normal renal cells. No alpha V was detected in Cak i-1 cells. The greatest adhesion of all cells occurred in the presence of a stimulatory anti-alpha(3) antibody, mediated by specific matrix proteins employed as substrates, while anti-beta(1) treatment dramatic ally inhibited cell attachment on collagen IV, plasma fibronectin, lam inin and merosin substrates. In addition, the mRNA expression of focal adhesion kinase (p125(FAK)) and paxillin were up-regulated (2.0-2.5 f old increase) in the metastatic Caki-1 cells over normal RCEC. The alt eration of integrin subunits alpha(2), alpha(3), alpha V, beta(1), as well as p125(FAK) and paxillin may contribute to the pathogenicity and /or metastatic propensity of renal epithelial tumors. The up-regulatio n of paxillin independently or in concert with p125(FAK) as shown in t his study indicates its significant role as a potential marker of meta stasis in renal carcinoma cells.