Research efforts are directed towards defining the repertoire of integrin cell adhesion receptors which are involved in neoplastic behavior in squamous cell neoplasms that affect human communication. Immunohistochemistry and reverse transcription-polymerase chain reaction are being used to define the expression of integrins during differentiation, tumor formation, invasion and metastasis of these neoplasms and their supporting stroma. Three integrins, a6b4, a2b1 and a3b1 are strongly expressed in a relatively larger suprabasilar population in neoplasms during the progressive acquisition of malignant potential and this expression is associated with cell proliferation. Keratinocytes, immortalized with HPV and transformed with v-ki-ras, have been studied to determine if increased integrin expression occurs with the step of immortalization or malignant transformation. Inhibitory monoclonal antibodies and synthetic inhibitors that specifically inhibit attachment of squamous cell carcinoma lines to extracellular matrix in vitro are being tested. An experimental model has been developed to test the effects of promising agents upon invasion and metastasis in vivo.