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 melanoma lines that failed to express the vitronectin receptor alpha v beta 3, but instead expressed alpha v beta 1. Levels of alpha v beta 1 expression were low on parental VUP cells so that iterative sorting by FACS, using an anti-alpha v antibody (13C2), was utilised to derive 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+) alpha v beta 1-expressing sublines with regard to adherence to collagen type I, collagen type IV or laminin substrata. However, adherence to vitronectin and fibrinogen correlated closely with alpha v beta 1 expression (35-42% adhesion for V(+) lines versus 6-8% adhesion for V- lines on vitronectin, for example). Utilising a high alpha v beta 1-expressing 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 effect on attachment or spreading of V + B2 on fibronectin whereas the combination of alpha 5 (PID6)- and alpha v(17E6)-blocking antibodies abrogated binding to fibronectin almost completely. This is the first report of an alpha v beta 1 integrin able to recognize vitronectin and fibrinogen, and also cooperate with alpha 5 beta 1 to mediate attachment to and spreading on fibronectin.
Marshall
J F
JF
Richard Dimbleby Department of Cancer Research/ICRF Laboratory, St Thomas' Hospital, London, UK.
Rutherford
D C
DC
McCartney
A C
AC
Mitjans
F
F
Goodman
S L
SL
Hart
I R
IR
D000906:Antibodies; D001667:Binding, Competitive; D002448:Cell Adhesion / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism; D010449:Peptide Mapping; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011233:Precipitin Tests; D016024:Receptors, Cytoadhesin / Q000378:metabolism*; D017469:Receptors, Fibronectin; D019030:Receptors, Vitronectin; D014407:Tumor Cells, Cultured
D000906:Antibodies; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D016023:Integrins; D010980:Platelet Membrane Glycoproteins; D016024:Receptors, Cytoadhesin; D017469:Receptors, Fibronectin; D019030:Receptors, Vitronectin; C094340:integrin alphavbeta1