Glycoprotein 90K/MAC‐2BP interacts with galectin‐1 and mediates galectin‐1–induced cell aggregation

Abstract

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. © 2001 Wiley‐Liss, Inc.

Expression and immunogenicity of a tumor‐associated antigen, 90K/Mac‐2 binding protein, in lung carcinoma

“…15,16 It was also found that M2BP serves as a ligand for galectin-1 and mediates the cell-aggregating activity by this lectin. 27 These characteristics allow us to assume that M2BP is responsible for metastatic activity of cancer cells. 28 On the other hand, M2BP is thought to play a part in cellular immune responses in hosts.…”

Induction of Mac-2BP by nerve growth factor is regulated by the PI3K/Akt/NF-κB-dependent pathway in the HEK293 cell line

“…Moreover, several reports have shown that the protein may function in cell adhesion processes. In particular, it has been demonstrated that Mac-2BP, as a ligand of galectin-1, -3, and -7, may promote homotypic cell-to-cell contacts (11,12), or may regulate cell adhesion by binding to cellular matrix proteins including β1-integrin, collagens, and fibronectins (13). Therefore, Mac-2BP may favor the establishment of new tumor colonies via enhancement of adhesive interactions between tumor cells and the extracellular matrix (14,15).…”

Galectins: Structures, Binding Properties and Function in Cell Adhesion

“…For example osteopontin from human bone shows only two N-glycans with binding sites which are partially blocked by 6-bound sialic acid (Ideo et al, 2003;Masuda et al, 2000;Stowell et al, 2008a). Another extracellular matrix protein interacting with galectin-1 and -3 is the Mac-2 binding protein or 90K antigen which influences adhesion processes (Sasaki et al, 1998;Tinari et al, 2001). The different ECM-proteins which are bound by galectins can interact with other ECMglycoproteins and/or integrins (Adams, 2001;Janik et al, 2010;Kariya et al, 2008;Singh et al, 2010).…”