The goal of this project is l) to identify and determine the role of cell adhesion molecules expressed by neoplastic and host cells during tumor progression of neoplasms affecting human communication, and 2) to determine if these molecules may serve as markers or targets for prevention, early diagnosis or therapy. To identify and determine the role of cell adhesion molecules expressed by neoplastic cells, expression of integrin cell adhesion molecules in human squamous papilloma and carcinoma tissues and cell lines were analyzed by immunoassays and immunoprecipitation. Increased expression of three integrins was found to be an early marker for diagnosis and prognosis. Expression was associated with the step of immortalization, and the function of these integrins was found to involve attachment to the extracellular matrix component laminin. The role of these integrins in metastasis will be determined by use of monoclonal antibodies and peptide inhibitors using an in vivo metastasis assay. To determine the role of integrins expressed by endothelial cells during attachment, metastasis formation and angiogenesis, the effect of antibody and peptide receptor inhibitors upon these processes will be tested using in vitro and in vivo assays of adhesion and metastasis. Promising markers or targets for therapy identified by these experimental studies may be suitable for evaluation in human clinical studies.
