Salatino, M. et al. Galectin-1 as a potential therapeutic target in autoimmune disorders and cancer. Expert Opin. Biol. Ther. 8, 45-57

Instituto de Biología y Medicina Experimental (IBYME), Laboratorio de Inmunopatología, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.
Expert opinion on biological therapy (Impact Factor: 3.74). 02/2008; 8(1):45-57. DOI: 10.1517/14712598.8.1.45
Source: PubMed


Galectin-1, a member of a family of highly conserved glycan-binding proteins, has emerged as a regulator of immune cell tolerance and homeostasis. This endogenous lectin widely expressed at sites of inflammation and tumour growth, has been postulated as an attractive immunosuppressive agent to restore immune cell tolerance and homeostasis in autoimmune and inflammatory settings. On the other hand, galectin-1 contributes to different steps of tumour progression including cell adhesion, migration and tumour-immune escape, suggesting that blockade of galectin-1 might result in therapeutic benefits in cancer. Recent findings implicating galectin-glycoprotein lattices as selective regulators of inflammatory responses have provided new insights into the understanding of the molecular bases of galectin-1-induced immunoregulation. Here the authors review the dual role of galectin-1 as a selective immunosuppressive agent in T helper (T(H))1 and T(H)17-mediated inflammatory/autoimmune disorders and a potential therapeutic target in cancer and metastasis.


Available from: Mariana Salatino, Jul 31, 2014
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    • "On the other hand, silencing of Gal-1 gene expression or antibody-mediated Gal-1 blockade suppressed tumor growth and/or metastasis and promoted T cell-mediated tumor rejection in a variety of cancers including melanoma, lung adenocarcinoma, pancreatic adenocarcinoma , Hodgkin's lymphoma, neuroblastoma, mammary adenocarcinoma , Kaposi's sarcoma, glioblastoma and ovary carcinoma [24,50–58]. Seeking for potential mechanisms that could explain the broad immunosuppressive activity of this b-galactosidebinding lectin [59], we found, in a model of autoimmune ocular inflammation, that Gal-1 therapy increased the frequency of Fox- p3 À Tr1 cells, which suppressed retinal disease when adoptively transferred into immunized mice [45]. Moreover, Foxp3 + Tregs were also expanded following administration of recombinant Gal-1 in a lupus-like model [60]. "
    [Show abstract] [Hide abstract] ABSTRACT: Programs that control immune cell homeostasis are orchestrated through the coordinated action of a number of regulatory cell populations, including regulatory T cells, regulatory B cells, myeloid-derived suppressor cells, alternatively-activated macrophages and tolerogenic dendritic cells. These regulatory cell populations can prevent harmful inflammation following completion of protective responses and thwart the development of autoimmune pathology. However, they also have a detrimental role in cancer by favoring escape from immune surveillance. One of the hallmarks of regulatory cells is their remarkable plasticity as they can be positively or negatively modulated by a plethora of cytokines, growth factors and co-stimulatory signals that tailor their differentiation, stability and survival. Here we focus on the emerging roles of galectins, a family of highly conserved glycan-binding proteins in regulating the fate and function of regulatory immune cell populations, both of lymphoid and myeloid origins. Given the broad distribution of circulating and tissue-specific galectins, understanding the relevance of lectin-glycan interactions in shaping regulatory cell compartments will contribute to the design of novel therapeutic strategies aimed at modulating their function in a broad range of immunological disorders.
    Full-text · Article · Sep 2015 · FEBS letters
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    • "In addition, compelling evidence amassed over recent decades indicates that galectin-1 upregulation can dramatically influence tumor progression given its pleiotropic roles in cell transformation [31], cell proliferation [21] [32], angiogenesis [14] [33], cell adhesion and invasiveness [34] [35] [36] [37], and immunosuppression [38] [39]. Each galectin-1 monomer contains six cysteine residues per subunit, conferring a strong sensitivity to oxidation [40] [41]. "
    [Show abstract] [Hide abstract] 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.
    Full-text · Article · Aug 2013 · Cancer Treatment Reviews
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    • "Another interesting aspect to take into account for the use of Gal-1 in cancer therapy is its role as a master regulator of the immune response. Indeed, downregulating Gal-1 expression inhibits migration and restores susceptibility to apoptosis and so to cytotoxic drugs, making its inhibition a promising target in cancer therapy (Salatino et al., 2008; Rabinovich, 2005). "
    Full-text · Chapter · Dec 2011
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