""""""""Altered glycosylation of glycolipids, glycoproteins, or proteoglycans are frequently observed in tumor tissues and cultured cancer cell lines. These changes have diagnostic use but also can contribute to the ability of tumor cells to grow, induce neovascularization, metastasize, and avoid host immune surveillance. We are primarily studying sulfated glycoconjugates and their interaction with extracellular matrix and cell surface adhesion molecules, including thrombospondin, laminin, and apolipoprotein E. Human small cell lung carcinoma cell lines are used to examine expression and function of novel sulfated glycolipids. These glycolipids interact with thrombospondin and contribute to adhesion of SCLC cells on a thrombospondin matrix. Endothelial cell heparan sulfate proteoglycans are used to examine the specificity of thrombospondin for binding to proteoglycans required for signaling by angiogenic growth factors. Heparin oligosaccharides are being used to define the molecular basis for interactions of heparin and heparan sulfate proteoglycans with two binding motifs on the thrombospondin molecule and on a second heparin-binding protein, apolipoprotein E. Inhibitors of these interactions are being tested for effects on angiogenesis and tumor growth.""""""""

National Institute of Health (NIH)
National Cancer Institute (NCI)
Intramural Research (Z01)
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Special Emphasis Panel (LP)
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National Cancer Institute Division of Clinical Sciences
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