Galactosyl receptor, a cell surface C-type lectin of normal and tumoral prostate epithelial cells with binding affinity to endothelial cells.
BACKGROUND: The mechanism of bone metastasis of prostate cancer involves the interaction of cell surface receptor(s) on cancer cells with ligand(s) on bone marrow endothelial cell surfaces. The rat galactosyl receptor gene generates two mRNA species by differential splicing: one species encodes a protein identical to the minor form of hepatocyte asialoglycoprotein receptor and displays a galactose/N-acetyl-galactosamine-recognition domain; the other encodes a protein with identical intracellular and transmembrane domains but with a different extracellular domain lacking the carbohydrate-recognition domain (CRD). Both proteins appear to coexist as a heterooligomer on the surface of normal mouse, rat, and human prostate epithelial cells and human prostate cancer cells, including the PC-3 cell line. The CRD of galactosyl receptor mediates adhesion of normal and tumoral prostate cells to the surfaces of a human bone marrow endothelial cell line. The use of inhibitors targeting the CRD would be very valuable in hindering the binding of prostate cancer cells to endothelial cells, thus decreasing the incidence of hematogenous metastasis to bone. METHODS: Molecular biology, immunohistochemistry, flow cytometry, and a cell aggregation assay were used to determine the expression and role of the galactosyl receptor in cell adhesion. RESULTS: Immunoblotting experiments demonstrated that each component of the heterooligomer has a mass of 54 kDa, ascribed in part to associated carbohydrates. An oligonucleotide probe showed the presence of both galactosyl receptor forms in rat prostate and testis, but not in liver, kidney, and spleen. Antibodies to the CRD and a segment of the nonhomologous extracellular domain of the galactosyl receptor blocked cell adhesion to endothelial cell monolayers. CONCLUSIONS: The galactosyl receptor provides a valuable target for the development and use of synthetic ligands capable of disrupting endothelial cell-prostate cancer cell interaction, the first step in prostate cancer bone metastasis.[1]References
- Galactosyl receptor, a cell surface C-type lectin of normal and tumoral prostate epithelial cells with binding affinity to endothelial cells. Kierszenbaum, A.L., Rivkin, E., Chang, P.L., Tres, L.L., Olsson, C.A. Prostate (2000) [Pubmed]
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