ENDOGENOUS LAMININ EXPRESSION AND METASTASIS

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Laminin, a high molecular weight glycoprotein found in basement membranes, has been shown to mediate the attachment of several types of cells to basement membrane (type IV) collagen. Our preliminary studies have shown a direct correlation between the expression of an endogenous laminin-like substance on the surface of murine tumor cells and metastatic potential. It is hypothesized that the expression of this substance contributes to metastasis, possibly by facilitating attachment of the metastasizing cells to basement membranes. The overall goal of this work is to provide direct evidence to show that the expression of cell surface laminin contributes to metastatic potential. Two approaches will be used to do this. In the first approach we will examine uncloned heterogeneous murine tumors for differences in expression of cell surface laminin, isolating and establishing laminin-positive and laminin-deficient cell lines from these populations. Three methods will be used to do this. These will include: (1)\complement-mediated cytotoxicity in the presence of affinity-purified antilaminin antibodies; (2)\flow cytometry; and (3)\collagen attachment. The laminin-positive and laminin-deficient cell lines isolated by these means will then be compared with regard to tumorigenicity and metastasis formation. In a second approach we will add exogenous laminin to the laminin-deficient cells. The laminin-treated cells will then be compared with untreated control cells with regard to in vivo behavior. The significance of this research lies in the fact that it will provide direct evidence to determine whether or not the expression or cell surface laminin by tumor cells contributes to their potential for malignancy. (A)