ALPHA(V)BETA(1) IS A RECEPTOR FOR VITRONECTIN AND FIBRINOGEN, AND ACTS WITH ALPHA(5)BETA(1) TO MEDIATE SPREADING ON FIBRONECTIN

We have shown previously that VUP was the only line out of ten human m elanoma lines that failed to express the vitronectin receptor alpha(v) beta(3), hot instead expressed alpha(v) beta(1). Levels of alpha(v) b eta(1) expression were low on parental VUP cells so that iterative sor ting by FACS, using an anti-cry antibody (13C2), was utilised to deriv e sublines with 8- to 10-fold higher amounts of cell surface alpha(v) beta(1). There was little difference between low (V-) and high (V+) al pha(v) beta(1)-expressing sublines with regard to adherence to collage n type I, collagen type IV or laminin substrata. However, adherence to vitronectin and fibrinogen correlated closely with alpha(v) beta(1) e xpression (35-42% adhesion for V(+) lines versus 6-8% adhesion for V-l ines on vitronectin, for example). Utilising a high alpha(v) beta(1)-e xpressing subline (V+B2) we have shown that binding to vitronectin and fibrinogen was inhibited specifically by function-blocking antibodies to alpha(v) (17E6 and 14D9) and beta(1) (A11B2). V(+) sublines spread more compared with V(-) sublines on both vitronectin and fibronectin, However, neither alpha(5)- nor alpha(v)-blocking antibodies had any e ffect on attachment or spreading of V+B2 on fibronectin whereas the co mbination of alpha(5) (PID6)- and alpha(v)(17E6)-blocking antibodies a brogated binding to fibronectin almost completely, This is the first r eport of an alpha(v) beta(1) integrin able to recognise vitronectin an d fibrinogen, and also cooperate with alpha(5) beta(1) to mediate atta chment to and spreading on fibronectin.