Benzyl-alpha-GalNAc inhibits sialylation of O-glycosidic sugar chains on CD44 and enhances experimental metastatic capacity in B16BL6 melanoma cells.
We examined the effect of benzyl-alpha-N-acetylgalactosamine (benzyl-alpha-GalNAc), which specifically inhibits the synthesis of O-linked oligosaccharides, on the expression of the peanut agglutinin (PNA)-binding sugar chains (Gal beta 1-3GalNAc) of CD44 and on its experimental metastatic ability in B16BL6 melanoma. Benzyl-alpha-GalNAc increased the PNA-binding, but not Concanavalin A (Con A), wheat germ agglutinin (WGA), and leukoagglutinating phytohemaagglutinin (L-PHA)-binding to the cell surface. Benzyl-alpha-GalNAc markedly increased the PNA-binding to CD44 by decreasing the sialylation of these sugar chains. The experimental metastatic ability of B16BL6 cells was enhanced in association with this modulation of the sugar chains. These findings suggested that unsialylated Gal beta 1-3GalNAc sugar chains on the cell surface and/or CD44 are involved in the metastatic process of B16BL6 melanoma cells. On the other hand, the known functions of CD44, such as adhesion to hyaluronate, fibronectin, collagen, and endothelial cells, as well as homotypic aggregation, were not affected by benzyl-alpha-GalNAc regardless of the enhancement of metastatic ability induced by this glycosylation inhibitor. CD44 might have other metastasis related functions that remain to be elucidated.
Nakano
T
T
Department of Pathology, Kanazawa Medical University, Ishikawa, Japan.
Matsui
T
T
Ota
T
T
D000116:Acetylgalactosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001593:Benzyl Compounds / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D003208:Concanavalin A / Q000378:metabolism; D006031:Glycosylation; D018960:Hyaluronan Receptors / Q000737:chemistry* / Q000378:metabolism; D037102:Lectins / Q000378:metabolism*; D008297:Male; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D019887:Peanut Agglutinin; D010835:Phytohemagglutinins / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014909:Wheat Germ Agglutinins / Q000378:metabolism
D001593:Benzyl Compounds; D018960:Hyaluronan Receptors; D037102:Lectins; D019887:Peanut Agglutinin; D010835:Phytohemagglutinins; D014909:Wheat Germ Agglutinins; D003208:Concanavalin A; C080739:benzyl-alpha-N-acetylgalactosamine; D019158:N-Acetylneuraminic Acid; D000116:Acetylgalactosamine