Role of the αvβ6 Integrin in Human Oral Squamous Cell Carcinoma Growth in Vivo and in Vitro

Abstract Expression of the αvβ6 integrin is strikingly upregulated in several types of carcinoma, including human oral squamous cell carcinoma (SCC). Employing a neutralizing monoclonal antibody to αvβ6, we investigated its role in cell adhesion, proliferation, migration, and in vivo growth of an invasive human SCC line, termed HSC-3. We found that αvβ6 is strictly required for HSC-3 cell growth in a three-dimensional collagen gel and also prominently contributes to cell migration in two different assay systems. In addition, the anti-αvβ6 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 by 59%. Histologically, antibody-treated tumors appeared less invasive than control tumors. Furthermore, intravenous application of a neutralizing antibody to the αv integrin subunit retarded HSC-3 tumor growth. These results point to a possible critical role of the αvβ6 integrin in controlling growth and invasion of human oral cancer cells.