ADHESION OF TUMOR-CELLS TO EXTRACELLULAR-MATRIX IS MEDIATED BY FIBRONECTIN

Tumor cell (TC) vessel wall adhesion is thougth to occur at specific sites of exposed extracellular matrix (ECM).To determine the role of fibronectin (FN) in TC/ECM adhesion,we measured; 1)TC adhesion to intact cultured endothelial cell monolayers (EC) or their ECMs,with or without incubation with a polyclonal antibody (Ab) to human FN, or a monoclonal antibody (Mab) to the cell binding site of FN (3E3);2)TC adhesion to EC or their exposed ECMs incubated with specific peptides against bacteria adhesion sites (I 133-79) or the peptide GRGDSP contained in the cell binding sites of several adhesive proteins.TC adhesion was measured as number of 111In-labeled A-549 adenocarcinoma cellsxlO /disc. ECMs were exposed by removing the ECs with N2 flow or EGTA treatment.There was 5.5±1x10 A-549/ EC covered disc (Table). Treatment of ECs with the Abs or peptides had no effect on TC adhesion.TC adhesion to the two ECM preparation were 42 ± 12 and 55±10 respectively.(Table).Blockage of the FN adhesive site by either Ab inhibited TC adhesion (p < 0.01). In contrast,blockage of the bacteria-adhesion site or incubation with GRGDSP had not significant effects in TC adhesion. The table shows the results (mearv±SEM (* p < 0.01).We conclude that TC adhesion to ECM but not to ECs,is dependent upon FN.