Disease relevance of LGALS3BP

• Levels of a 90-kDa tumor associated protein, designated 90K (gene symbol LGALS3BP), have been found elevated in the serum of patients with cancer and in those infected by the human immunodeficiency virus (HIV) [1].
• 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 [2].
• 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 [2].
• High expression levels of 90K are associated with a shorter survival, the occurrence of metastasis or a reduced response to chemotherapy in patients with different types of malignancy [3].
• To elucidate the role of TAA90K in colon cancer, we examined its expression and function in human colon tumors and colon carcinoma cell lines [4].

High impact information on LGALS3BP

• Antisera also react with the larger component of cytochrome b recently purified from neutrophil plasma membranes as a complex of glycosylated 90K and non-glycosylated 22K polypeptides [5].
• The antigen receptor on the surface of human T lymphocytes, which consists of a heterodimer of relative molecular mass (Mr) 90,000 (90K) (alpha- and beta-chains), is associated with the T3 antigen (gamma = 25K, delta = 20K and epsilon = 20K) [6].
• This distinguishes cell adhesion of M2BP from that of laminin and excludes involvement of lactose-binding galectin-3 [7].
• The 43K and 58K proteins appeared to co-purify with the receptor-containing membranes while the 90K protein did not [8].
• This finding could explain the lack of response in lymphoma patients with high 90K serum levels [9].

Chemical compound and disease context of LGALS3BP

• The tumor-derived antigen 90K (Mac-2 BP) is a widely expressed, secreted glycoprotein found in the serum of healthy individuals and at elevated levels in the serum of patients with breast cancer and other types of cancer [10].
• Expression of tumor-associated 90K-antigen in human breast cancer: no correlation with prognosis and response to first-line therapy with tamoxifen [11].
• Finally, an increase in serum 90K levels was observed in 3 patients with advanced breast cancer receiving a short course of rIFN-alpha 2b (Intron A) [12].
• Using precautions to limit proteolysis, virus particles 34 nm in diameter were banded in a Nycodenz gradient together with the nine disease-associated dsRNAs and three proteins of M(r) 120K, 115K and 90K [13].
• Lamp-1 and Lamp-2 immunoreactivity was present at the luminal side of the ductal carcinoma cells whereas Mac-2-BP immunoreactivity was diffusely spread over the whole cytoplasm and the nucleolus of ductal carcinoma cells [14].

Biological context of LGALS3BP

• The mechanisms underlying the prognostic significance of 90K and galectins in cancer are far from being understood, although they may be related to the ability of these proteins to interact and, to some extent, modulate cell-cell and cell-matrix adhesion and apoptosis [3].
• Thus, a possible mechanism by which TAA90K may contribute to colon cancer progression is by modulating tumor cell adhesion to extracellular proteins, including galectin-3 [4].
• As expected, binding of TAA90K to galectin-3 was dependent on carbohydrate since it was inhibitable by lactose and asiolofetuin, and a TAA90K-His glycoform purified from HT-29 cells treated with the glycosylation inhibitor 1-deoxymannojirimycin bound poorly to galectin-3 [4].
• Mac-2-binding protein also induced homotypic cell aggregation, which was inhibited by lactose or Fab' fragments of an anti-galectin-3 antibody [15].
• Domain 2 (BTB/POZ domain) is thus identified as the dimerization domain of M2BP, because it has been formerly shown that recombinant domain 1 is monomeric [16].

Anatomical context of LGALS3BP

• Western analysis suggests that Mac-2-BP is found in serum, semen, saliva, urine, and tears, in addition to breast milk [17].
• Recombinant Mac-2-BP was expressed in Cos cells and secreted as a high molecular weight complex [17].
• 90K appears to be implicated in immune response associated with natural killer (NK) and lymphokine-activated killer (LAK) cell cytotoxicity [1].
• Based on the current data, we propose a model in which 90K activates accessory cells, resulting in the secretion of cytokines and the expression of adhesion molecules, which in turn act as costimulatory signals for T-cell activation [18].
• Enhanced 90K level effects are both localized and systemic and involve induction of ICAM-1 and VCAM-1 in the tumor endothelium [19].

Associations of LGALS3BP with chemical compounds

• The glycoprotein 90K was originally described as a tumor-secreted antigen and subsequently found to have immunostimulatory activity as well as other possible functions [2].
• In a solid-phase binding assay, human recombinant galectin-1 bound immobilized human recombinant 90K in a fashion that was inhibitable by lactose [2].
• However, Mac-2-BP did slow the neutralization of LPS mediated by plasma lipoprotein [20].
• Cloning and characterization of a human Mac-2-binding protein, a new member of the superfamily defined by the macrophage scavenger receptor cysteine-rich domain [17].
• The increase of 90K expression was due to de novo protein synthesis since cycloheximide, added within 3 hr of the beginning of rIFN-alpha 2b stimulation treatment, completely abolished the effect of rIFN-alpha 2b [12].

Regulatory relationships of LGALS3BP

• This 90K-induced upregulation of ICAM-1 expression was accompanied by an increased accessory function of the monocytes, demonstrated by their ability to support ConA-induced activation of peripheral blood T cells [18].
• Our findings suggest that Mac-2BP is induced by hTERT, and that it may prove to be a useful prognostic marker for the detection of malignant progression of metastatic stomach cancers [21].

Other interactions of LGALS3BP

• Experiments with purified Mac-2-BP showed that this protein alone neither enabled responses of CD14-bearing cells to LPS nor blocked the ability of plasma to enable responses of CD14-bearing cells to LPS [20].
• This procedure isolated not only LBP but also a serum protein known as Mac-2-binding protein (Mac-2-BP), a 97 kDa species without a known function [20].
• In addition, expression of ICAM-1 was increased on a human monocytic cell line cultured with purified 90K in the absence of any other stimulus [18].
• These compounds showed a differential ability to inhibit binding of galectin-1 and/or galectin-3 to the highly glycosylated protein 90K in solid-phase assays [22].
• 90K, also known as Mac-2 binding protein, is a secreted glycoprotein that binds galectins, beta1-integrins, collagens, and fibronectin, and has some relevance in cell-cell and cell-extracellular matrix adhesion [23].

Analytical, diagnostic and therapeutic context of LGALS3BP

• Expression of 90K was confirmed by ELISA [23].
• Northern blotting analysis revealed differences in the transcriptional regulation of galectin-3 and Mac-2-binding protein [15].
• Ultracentrifugation revealed that M2BP-1,2 is homogeneously dimeric in the nanomolar range reflecting the properties of intact M2BP [16].
• The gene encoding Mac-2-BP was cloned from a cDNA bank of a human monocytic cell line, using degenerate PCR primers based on the protein sequence [17].
• Using fluorescence in situ hybridization the full length 90K cDNA has been localized to chromosome 17q25 [1].

References