Glycoprotein 90K/MAC-2BP interacts with galectin-1 and mediates galectin-1-induced cell aggregation.
The glycoprotein 90K was originally described as a tumor-secreted antigen and subsequently found to have immunostimulatory activity as well as other possible functions. This protein interacts with an endogenous lectin, galectin-3, and may play a role in tumor metastasis through this interaction. Because 90K is heavily glycosylated, it may also interact with other members of the galectin family, which would contribute to the multifunctionality of 90K. To test this possibility, we studied the recognition of 90K by galectin-1, which, like galectin-3, has been associated with neoplastic transformation. In a solid-phase binding assay, human recombinant galectin-1 bound immobilized human recombinant 90K in a fashion that was inhibitable by lactose. Galectins 1 and 3 appeared to bind to separate sites on 90K because they did not affect the binding of each other. The dissociation constant of galectin-1 to 90K was on the order of 10(-7) M. Galectin-1 also induced aggregation of a human melanoma cell line, A375, in a carbohydrate-dependent manner, and this appeared to be mediated, at least in part, by 90K expressed on A375 cells, since it was inhibitable by a specific anti-90K monoclonal antibody. We conclude that 90K interacts with both galectin-1 and galectin-3 and both interactions contribute to the formation of multicell aggregates. Because both of these galectins as well as 90K are often over-expressed in neoplasm, these interactions may occur in the setting of various carcinomas and contribute to their progression and metastasis.
Tinari
N
N
Department of Oncology and Neurosciences, Università G. D'Annunzio, Chieti, Italy.
Kuwabara
I
I
Huflejt
M E
ME
Shen
P F
PF
Iacobelli
S
S
Liu
F T
FT
D016475:3T3 Cells; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002449:Cell Aggregation; D037483:Galectin 1; D037502:Galectin 3; D006023:Glycoproteins / Q000378:metabolism*; D006388:Hemagglutinins / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000473:pathology; D051379:Mice; D008970:Molecular Weight; D014407:Tumor Cells, Cultured
D000943:Antigens, Differentiation; D037483:Galectin 1; D037502:Galectin 3; D006023:Glycoproteins; D006388:Hemagglutinins