THE ROLE OF BETA-1-INTEGRINS IN ADHESION OF 2 BREAST-CARCINOMA CELL-LINES TO A MODEL ENDOTHELIUM

Interactions between tumour cells and the endothelium are vital to the formation of haematogenous metastases. Binding to model endothelium o f one oestrogen receptor positive breast carcinoma cell line (MCF-7) a nd one receptor negative line (HS578T) was examined in vitro together with endothelial retraction induced by these tumour cells. Adhesion wa s inhibited by monoclonal antibodies specific for the VLA integrins an d by peptides containing the RGD motif which is commonly recognised as a ligand by the VLA adhesion molecules. However, binding of the two t umour cell lines was inhibited by monoclonal antibodies specific for d ifferent VLA molecules; anti-alpha 6 beta 1 inhibited MCF-7 adhesion b ut anti-alpha 5 beta 1 inhibited Hs578T. These results were consistent with flow cytometric quantification of the expression of these VLA in tegrins on the surfaces of the two tumour cell lines. Enzyme-linked im munosorbent assays (ELISA) demonstrated that lamimin was present on th e endothelial cell surface but collagen IV was absent, ELISA failed to detect increased exposure of the subendothelial matrix during the fir st hour after addition of either cancer cell type. This was supported by assays which demonstrated maintenance of the endothelial permeabili ty barrier during this period. Slight endothelial retraction was detec ted within 2 hours of the addition of tumour cells, It is concluded th at binding between tumour cells and confluent endothelium is inhibited by the blockade of adhesion molecules which are normally associated w ith interactions between the cell and the subendothelial matrix. Tumou r cell to matrix interactions rather than direct tumour to endothelial cell adhesion may be the limiting step in tumour cell binding to the endothelium.