Role of the alpha(v)beta6 integrin in human oral squamous cell carcinoma growth in vivo and in vitro.
Expression of the alpha(v)beta6 integrin is strikingly upregulated in several types of carcinoma, including human oral squamous cell carcinoma (SCC). Employing a neutralizing monoclonal antibody to alpha(v)beta6, 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 alpha(v)beta6 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-alpha(v)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 by 59%. Histologically, antibody-treated tumors appeared less invasive than control tumors. Furthermore, intravenous application of a neutralizing antibody to the alpha(v) integrin subunit retarded HSC-3 tumor growth. These results point to a possible critical role of the alpha(v)beta6 integrin in controlling growth and invasion of human oral cancer cells.
Xue
H
H
Lung Biology Center, Department of Medicine, University of California, San Francisco, California 94143-0854, USA.
Atakilit
A
A
Zhu
W
W
Li
X
X
Ramos
D M
DM
Pytela
R
R
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D000951:Antigens, Neoplasm; D015197:Carcinogenicity Tests; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D004195:Disease Models, Animal; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy; D017469:Receptors, Fibronectin / Q000502:physiology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000906:Antibodies; D000951:Antigens, Neoplasm; D005353:Fibronectins; D016023:Integrins; D017469:Receptors, Fibronectin; C073878:integrin alphavbeta6