Galectins: matricellular glycan-binding proteins linking cell adhesion, migration, and survival

Instituto de Química y Fisicoquímica Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1123, Buenos Aires, Argentina.
Cellular and Molecular Life Sciences CMLS (Impact Factor: 5.86). 08/2007; 64(13):1679-700. DOI: 10.1007/s00018-007-7044-8
Source: PubMed

ABSTRACT Galectins are a taxonomically widespread family of glycan-binding proteins, defined by at least one conserved carbohydrate-recognition domain with a canonical amino acid sequence and affinity for beta-galactosides. Because of their anti-adhesive as well as pro-adhesive extracellular functions, galectins appear to be a novel class of adhesion-modulating proteins collectively known as matricellular proteins (which include thrombospondin, SPARC, tenascin, hevin, and disintegrins). Accordingly, galectins can display de-adhesive effects when presented as soluble proteins to cells in a strong adhesive state. In this context, the de-adhesive properties of galectins should be considered as physiologically relevant as the proadhesive effects of these glycan-binding proteins. This article focuses on the roles of mammalian galectins in cell adhesion, spreading, and migration, and the crossregulation of these functions. Although careful attention should be paid when examining individual galectin functions due to overlapping distributions, these intriguing glycan-binding proteins offer promising possibilities for the treatment and intervention of a wide variety of pathological processes, including cancer, inflammation, and autoimmunity.

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    • "Galectins (Gals), a family of mammalian lectins, are involved in a wide spectrum of biological processes such as proliferation, apoptosis , adhesion, migration and cytokine secretion, among others (Elola et al. 2007; Liu and Rabinovich 2010). Moreover, Gals have immune regulatory functions and play important roles in the homeostasis of the immune system (Norling et al. 2009; Cattaneo et al. 2011). "
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    ABSTRACT: Galectins (Gals), a family of mammalian lectins, play diverse roles under physiological and pathological conditions. Here we analyzed the tandem-repeat Gal-8 synthesis, secretion and effects on the endothelium physiology. Gal-8M and Gal-8 L isoforms were secreted under basal conditions by human microvascular endothelial cells (HMEC-1). However, expression and secretion of the Gal-8M isoform, but not Gal-8 L, were increased in response to bacterial lipopolysaccharide (LPS) stimulus and returned to control values after LPS removal. Similarly, cell surface Gal-8 exposure was increased after stimulation with LPS. To evaluate Gal-8 effects on the endothelium physiology, HMEC-1 cells were incubated in the presence of recombinant Gal-8M. Pretreated HMEC-1 cells became pro-adhesive to human normal platelets, indicating that Gal-8 actually activates endothelial cells. This effect was specific for lectin activity as it was prevented by the simultaneous addition of lactose, but not by sucrose. Endothelial cells also increased their exposition of von Willebrand factor after Gal-8 treatment, which constitutes another feature of cell activation that could be, in turn, responsible for the observed platelet adhesion. Several pro-inflammatory molecules were abundantly produced by Gal-8 stimulated endothelial cells: CXCL1 (GRO-α), GM-CSF, IL-6 and CCL5 (RANTES), and in a lower degree CCL2 (MCP-1), CXCL3 (GRO-γ) and CXCL8 (IL-8). In agreement, Gal-8M induced NFκB phosphorylation. Altogether, these results not only confirm the pro-inflammatory role we have already proposed for Gal-8 in other cellular systems, but also suggest that this lectin is orchestrating the interaction between leukocytes, platelets and endothelial cells.
    Glycobiology 06/2014; 24(10). DOI:10.1093/glycob/cwu060 · 3.75 Impact Factor
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    • "These ''dual'' effects may be associated with a competitive interaction of critical ECM components/cell surface proteins with galectin-1, and the coexpression of other galectin members with biologically opposite effects. It is worth noting that the presence of soluble or immobilized galectin-1 in the intracellular space can be crucial for the final outcome in galectin-1-related cell adhesion and invasion [55]. "
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    ABSTRACT: Galectins belong to a family of carbohydrate-binding proteins with an affinity for β-galactosides. Galectin-1 is differentially expressed by various normal and pathologic tissues and displays a wide range of biological activities. In oncology, galectin-1 plays a pivotal role in tumor growth and in the multistep process of invasion, angiogenesis, and metastasis. Evidence indicates that galectin-1 exerts a variety of functions at different steps of tumor progression. Moreover, it has been demonstrated that galectin-1 cellular localization and galectin-1 binding partners depend on tumor localization and stage. Recently, galectin-1 overexpression has been extensively documented in several tumor types and/or in the stroma of cancer cells. Its expression is thought to reflect tumor aggressiveness in several tumor types. Galectin-1 has been identified as a promising drug target using synthetic and natural inhibitors. Preclinical data suggest that galectin-1 inhibition may lead to direct antiproliferative effects in cancer cells as well as antiangiogenic effects in tumors. We provide an up-to-date overview of available data on the role of galectin-1 in different molecular and biochemical pathways involved in human malignancies. One of the major challenges faced in targeting galectin-1 is the translation of current knowledge into the design and development of effective galectin-1 inhibitors in cancer therapy.
    Cancer Treatment Reviews 08/2013; 40(2). DOI:10.1016/j.ctrv.2013.07.007 · 6.47 Impact Factor
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    • "Several tumour markers were studied in a trial to improve the detection rate of bladder cancer, using non-invasive techniques [3], but none have yet taken the place of urinary cytology, which showed up to 85% sensitivity and 87% specificity for high-grade tumours [10]. G-3, an intracellular secreted carbohydrate-binding protein, acts as a regulator of the cell cycle, inflammation , immune responses, cell adhesion, and cell signalling events [11] [12]. Anti-apoptotic activity was attributed as a possible cause for the involvement of G-3 in carcinogenesis [13]. "
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    ABSTRACT: Objective To evaluate serum levels of galectin-3 (G-3) in patients with bladder cancer and a control group, as a potential diagnostic and prognostic serum tumour marker. Patients and methods Between November 2012 and January 2013, 55 patients (median age 58 years) were enrolled into three groups, i.e., a control, those with transitional cell carcinoma (TCC) or those with squamous cell carcinoma (SCC). The serum G-3 level was measured the night before cystoscopy. The levels of G-3 levels were correlated with tumour type, stage and grade, and in relation to levels in normal urothelium. The results were analysed statistically using the Mann–Whitney U-test, the Kruskal–Wallis test and the receiver operating characteristic curve, as appropriate. Results The median serum G-3 level was 100, 720 and 920 pg/mL in the control, TCC and SCC groups, respectively, with very significantly greater G-3 levels in both the TCC and SCC groups than in the control group. Patients with high-grade TCC had a statistically significantly greater serum G-3 level than those with low-grade tumours, as did those with muscle-invasive TCC than those with Ta tumours. Conclusions The level of G-3 can aid as a diagnostic marker in patients with either TCC or SCC of the bladder, but the prognostic significance of G-3 remains to be confirmed.
    01/2013; 12(2). DOI:10.1016/j.aju.2013.10.004
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