The long term goals of this study are to identify and characterize the molecules involved in the intercellular adhesion of teratocarcinoma stem cells, to describe their mode of action in adhesion, and their possible role during stem cell differentiation. The value of undertaking this study using teratocarcinoma stem cells is underscored by the implication that aggregation is a prelude to differentiation in this system. Studying the basis of adhesion and differentiation of teratocarcinoma stem cells is of particular interest because the stem cells lose their tumorigenecity when they differentiate, thereby providing a model for evaluating the regulation of the neoplastic state. In preliminary studies based upon the lectin hypothesis of cell-cell recognition, we have described a fucan-mannan specific lectin activity, present on the surface of the stem cells, which appears to mediate a divalent cation-independent component of cell adhesion. We have recently identified the protein responsible for this activity.
The specific aims of this proposal include employing antibody specific to the lectin in studies designed to 1) determine the cell type specificity of expression of the lectin, 2) verify the role of the protein in stem cell adhesion, and 3) determine if this protein is involved in stem cell differentiation. In addition we propose to identify an endogenous carbohydrate-containing receptor for the lectin, and to decipher the mode of action of these interacting components during cell adhesion. The lectin receptor may be found among the previously described stem cell glycoconjugates reported to contain terminal fucose. The tissue specificity of the divalent cation-dependent and the divalent cation-independent systems of adhesion will be determined and the role of extracellular multicomponent particles as aggregation promoters will be evaluated. These experiments will provide detailed information on the moelcular mechanism of the intercelluar adhesion of teratcarcinoma stem cells.
