Role of the alpha v beta 6 integrin in human oral squamous cell carcinoma growth in vivo and in vitro

Expression of the alphav beta6 integrin is strikingly upregulated in severa l types of carcinoma, including human oral squamous cell carcinoma (SCC). E mploying a neutralizing monoclonal antibody to alphav beta6, we investigate d its role in cell adhesion, proliferation, migration, and in vivo growth o f an invasive human SCC line, termed HSC-3. We found that alphav beta6 is s trictly required for HSC-3 cell growth in a three-dimensional collagen gel and also prominently contributes to cell migration in two different assay s ystems. In addition, the anti-alphav beta6 antibody inhibited the invasive growth of HSC-3 cells transorally injected into nude mice. In the presence of the coinjected antibody, the average tumor size at 10 days was reduced b y 59%. Histologically, antibody-treated tumors appeared less invasive than control tumors. Furthermore, intravenous application of a neutralizing anti body to the av integrin subunit retarded HSC-3 tumor growth. These results point to a possible critical role of the alphav beta6 integrin in controlli ng growth and invasion of human oral cancer cells. (C) 2001 Academic Press.