CELL ADHESION IN NEOPLASIA AFFECTING HUMAN COMMUNICATION

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Summary of Work: The purpose of this project is to elucidate the molecular mechanisms of cell adhesion and recognition necessary for growth and migration of neoplastic and supporting cells in squamous cell neoplasms of the upper aerodigestive tract in order to develop approaches for pharmacologic and molecular prevention and therapy. A repertoire of integrin cell adhesion molecules that are overexpressed by squamous cell carcinomas and by the endothelial cells that form the vascular blood supply has been characterized by immunobiochemical and immunohistochemical methods. The ability of specific antibodies and small molecule receptor antagonists of these integrin receptors to inhibit attachment and growth of tumor and endothelial cells in vitro and in vivo have been the subject of ongoing investigations. The attachment of tumor cells to laminin, the extracellular matrix produced by the tumors, was shown to be predominantly due to three integrin receptors using specific antibodies in vitro. Studies to evaluate whether these receptors play an important role in tumor development and may be suitable targets for therapy await the development of small molecule inhibitors to each of these receptors. In studies using endothelial integrin receptor antagonists, members of the integrin receptor family appear to be important in the growth and migration of endothelial cells during tumor induced neoangiogenesis. In preliminary experiments, endothelial integrin receptor antagonists were found to inhibit the growth of squamous cell carcinomas in vivo. Further studies will be needed to determine optimal formulation, dose and route as well as toxicity before use in clinical trials may be undertaken.