Inhibition of selectin-dependent tumor cell adhesion to endothelial cells and platelets by blocking O-glycosylation of these cells.
Expression of sialosyl-Le(x) (SLe(x)) and sialosyl-Le(a) (SLe(a)) on tumor cell lines HL60, Colo205, and U937 was greatly suppressed by application of benzyl-alpha-GalNAc for inhibition of O-linked carbohydrate chain extension, which resulted in reduced adhesion of tumor cells to activated endothelial cells or platelets mediated by ELAM-1 (E-selectin) or GMP-140 (P-selectin). Inhibitors or modifiers of N-glycosylation had no effect on expression of SLe(x) or SLe(a) in these tumor cells. These findings suggest the possibility that targeting of O-glycosylation inhibitors or modifiers to tumor cells may effectively suppress metastatic potential.
Kojima
N
N
Biomembrane Institute, Seattle, WA 98119.
Handa
K
K
Newman
W
W
Hakomori
S
S
D000116:Acetylgalactosamine / Q000031:analogs & derivatives*; D000911:Antibodies, Monoclonal; D001792:Blood Platelets / Q000502:physiology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D003110:Colonic Neoplasms; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000502:physiology*; D005434:Flow Cytometry; D006031:Glycosylation; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D007983:Lewis Blood Group Antigens / Q000502:physiology*; D016403:Lymphoma, Large B-Cell, Diffuse; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007983:Lewis Blood Group Antigens; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D000116:Acetylgalactosamine