title: Inhibition of integrin mediated cell adhesion of human head and neck squamous cell carcinoma to extracellular matrix laminin by monoclonal antibodies.
abstract: We recently reported that three members of the integrin family of cell adhesion molecules, designated alpha 2 beta 1, alpha 3 beta 1, and alpha 6 beta 4, are expressed at increased levels within the tumors and cell lines of patients with SCC. These three integrins have been reported to serve as receptors for laminin isoforms, and we also previously observed that laminins are secreted by SCC cell lines isolated from patients. In this study, the expression and localization of the three integrins and laminin in situ was evaluated in ten tumor specimens from patients with SCC by immunohistochemistry using integrin subunit-specific monoclonal antibodies. The ability of the antibodies to inhibit laminin attachment of a human squamous cell carcinoma line was determined by in vitro cell adhesion assay. Laminin and the three integrins were co-localized along the invasive border of the tumor parenchyma in 10/10 patient tumor specimens. Attachment of the UM-SCC-38 cell line to laminin was strongly inhibited by specific mAbs to alpha 2 and alpha 6 integrin subunits alone, or completely using a combination of alpha 2, alpha 3, and alpha 6 subunit specific mAbs. The co-localization of the three abnormally expressed integrins and laminin in patient tumor specimens indicates the potential for interaction of these receptors and ligand in vivo. The results of the cell adhesion assays using a patient SCC cell line that expresses the same repertoire of integrins confirms that SCC attach to laminin isoforms primarily through the alpha 2, alpha 3 and alpha 6 subunit-containing integrins. These findings provide a basis for undertaking experimental studies to obtain small molecule receptor antagonists to determine the role of these integrins in tumor formation, growth, invasion and metastasis in vivo.
authors.affiliation: UNIV MICHIGAN,CTR CANC,LAB HEAD & NECK CANC BIOL,DEPT OTOLARYNGOL HEAD & NECK SURG,ANN ARBOR,MI 48109.
authors.forename: C
authors.initials: C
authors.lastname: Vanwaes
authors.forename: D
authors.initials: D
authors.lastname: Surh
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: T
authors.initials: T
authors.lastname: Carey