The Mechanism of Lectin-Mediated Adhesion of Human Ovarian Carcinoma Cells
Tumor invasion, dissemination and the subsequent formatlon of metastatic foci derive from alteratlons in tumor cell adheslveness. Lectins and other intercellular adhesion molecules (ICAMs) are involved in establishlng adhesion between tumor cells, vascular endothelial cells and the basement membrane. Galaptin, an endogenous lectin with affinity for galactose containing oligosaccharides, is present in the extracellular matrlx (ECM) and participates in the binding of A121 human ovarian carcinoma cells to the ECM. The specificity for galactose was demonstrated by inhibiting binding with lactose and by pretreating A121 cells with β-galactosidase. We have now carried out studies to identlfy the cellular glycoprotein(s) that are responslble for binding A121 cells to galaptin. Our results indicate that the galaptin receptor on the ovarian tumor cell surface is a hlghly glycosylated, lysosome-associated membrane protein (lamp). A series of membrane sugar analogs has been deslgned and synthesized as potential modulators of the galaptin receptor. One analog, 2-acetamldo-1, 4, 6-tri-0-acetyl-3-deoxy-3-fluoro-glucosamine (CD 89029), was found to specifically inhibit glycoprotein biosynthesls. As a result of this inhibition, tumor cells treated with CD 89029 decreased their adhesion to the ECM. These studies show that tumor cell adhesion is medlated by specific endogenous lectins and their cell surface glycoconjugate receptors (i.e. lamp), and that appropriate sugar analogs can serve as potential Inhibitors of metastatic spread.
KeywordsA121 Cell Tumor Cell Adhesion Roswell Park Cancer Institute Human Ovarian Carcinoma Cell Endogenous Lectin
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