Cell surface adhesion receptors may be considered tumor- associated antigens in a true sense, since they implement several important traits of the malignant phenotype. It has been proposed that, in order to invade surrounding tissues and to metastasize, tumor cells guide themselves by specifically recognizing and attaching to extracellular matrix components. Such recognition mechanisms appear to be analogous to those utilized by normal cells during normal tissue development, and are thought to involve surface adhesion receptors for matrix components. Recently, the cell surface receptors for several extracellular matrix and plasma adhesive proteins have been identified at a molecular level. An important finding was that these receptors constitute a family of structurally homologous heterodimers, termed the integrins. Integrins appear to be expressed in a tissue-specific and developmentally-regulated fashion, and they likely account for the majority of adhesive properties of cells. However, the role of integrins in the biology of tumor cells has not been determined yet. The goal of this project is to determine the molecular mechanisms by which adhesion receptors of the integrin type may govern all or some of the invasive properties of carcinoma cells. To this end, we will identify integrin molecules expressed by a select panel of carcinoma cells and, by isolating their corresponding cDNA clones, will determine their primary structures. Based on this information, we will construct highly discriminating antibody and nucleic acid probes. These probes will then be exploited for the generation of integrin-deficient mutant carcinoma cells, to be tested in vitro and in vivo for their adhesive and invasive properties. It is hoped that these results will clarify correlations between integrin expression and invasive properties of carcinoma cell. This information will contribute to our general understanding of the molecular basis for the malignant behavior of tumor cells, and will hopefully offer new avenues to finding effective ways to control cancer cell growth.
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