Integrins alpha 5 beta 1, alpha v beta 1, and alpha v beta 6 collaborate in squamous carcinoma cell spreading and migration on fibronectin

The expression of alpha v beta 6 fibronectin/tenascin receptor integrin is induced in malignant transformation of oral epithelium. In this study, we d emonstrate the contribution of alpha v beta 6 as well as other fibronectin receptor integrins in squamous cell carcinoma (SCC) cell adhesion and migra tion. Of 11 SCC cell lines isolated from the head and neck area, 8 (73%) ex pressed alpha v beta 6 integrin an the cell surface. Three cell lines were chosen for further functional experiments: 1 with relatively high, 1 with m oderate, and 1 with minimal surface expression of alpha v beta 6 integrin. In addition to alpha v beta 6, all 3 cell lines expressed alpha 5 beta 1 an d alpha v beta 1 fibronectin receptor integrins. Function-blocking experime nts with inhibitory anti-integrin antibodies showed that all these three in tegrins were functional in SCC cell spreading on fibronectin. Integrin alph a v beta 6, however, was not used as a primary but as an alternative fibron ectin receptor by SCC cells, as the inhibitory anti-beta 6 integrin antibod y alone had no effect on spreading. In migration, however; alpha v beta 6, alpha 5 beta 1, and alpha v beta 1 integrins were all used in cooperation. The presence of alpha v beta 1 integrin in SCC cells is a novel finding as is its contribution to SCC cell migration. When one or two of these three r eceptors were blocked, the cells demonstrated an adaptive ability to remain migratory using integrins that were not targeted by antibodies. Utilizatio n of a combination of receptors of different affinities may be beneficial f or SCC cell migration versatility. (C) 2000 Academic Press.