The glioma-mesenchymal extracellular matrix glycoprotein, GMEM, is a novel tumor-associated extracellular matrix protein. It is distinctive among extracellular matrix molecules in its restricted distribution in normal tissues and associations with the neovasculature of solid tumors and absence in normal blood vessels. GMEM has cell attachment-promoting activity which can be inhibited by -Arg-Gly-Asp- peptides and interacts with a cell surface receptor. The selective expression of GMEM, its association with the tumor neovasculature and cell adhesion activity indicates a selective role in cell-matrix interactions and may indicate a role in tumor angiogenesis. The role of GMEM in cell-matrix interactions will be examined through an analysis of intermolecular and cell-receptor interactions and analysis of GMEM expression and its association with vascular proliferation. We will: 1) clone and sequence GMEM cDNA from a fibroblast cDNA lambda gtll expression library. From the cDNA sequence we will obtain the complete amino acid sequence of GMEM. 2) GMEM mRNA expression and structure, and genomic structure will be examined using GMEM cDNA probes. mRNA expression will be examined in cell lines and the levels, number and size of homologous or related mRNA determined. 3) The intermolecular interactions of GMEM with other matrix components will be examined. The cell binding site and other possible binding sites will then be mapped on the GMEM polypeptide using bacterial expression of cDNA deletion libraries coding for deletion polypeptides. 4) Identification and characterization of the GMEM cell surface receptor will be made. The relationship of the cell receptor to other adhesion receptors will be examined using anti- receptor antibodies and analysis of receptor binding to adhesion proteins. 5) Cells made phenotypically GMEM- by transfection and expression of GMEM antisense RNA will be compared with GMEM+ parental cell lines and will be used to examine the role of GMEM in cell adhesion and association with angiogenesis in in vitro cell attachment assays and in vivo assays of tumor angiogenesis on chorio-allantoic membranes. These approaches to the study of GMEM will provide a basis for understanding the biological role of this novel molecule in normal and tumor development.
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