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.

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Available from: Mariana Salatino, Jul 31, 2014
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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]. "
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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 · 7.59 Impact Factor
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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). "

    Pancreatic Cancer - Molecular Mechanism and Targets, 12/2011; , ISBN: 978-953-51-0410-0
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    • "Galectin-1 is becoming widely recognized as an important lectin protein with significant roles in tumor progression and one of the roles of galectin-1 is its contribution to tumor cell evasion of immune cell surveillance [38, 39]. Galectin-1 has been shown to directly suppress T cell immunity by inducing T cell apoptosis [38], inhibiting T cell activation [40] and promoting regulatory T cell function [41]. "
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    ABSTRACT: Cancer cells produce galectin-1 as a tumor promoting protein. Thiodigalactoside (TDG) as a non-metabolised small drug, is shown to suppress tumor growth by inhibiting multiple cancer enhancing activities of galectin-1, including immune cell dysregulation, angiogenesis and protection against oxidative stress. Thus, using B16F10 melanoma and 4T1 orthotopic breast cancer models, intratumoral injection of TDG significantly raised the levels of tumor-infiltrating CD8+ lymphocytes and reduced CD31+ endothelial cell content, reducing tumor growth. TDG treatment of tumors in Balb/c nude mice (defective in T cell immunity) reduced angiogenesis and slowed tumor growth by a third less than in immunocompetent mice. Knocking down galectin-1 expression (G1KD) in both cancer cell types significantly impeded tumor growth and the sensitivity of the G1KD tumors to TDG was severely reduced, highlighting a specific role for galectin-1. Endothelial cells were protected by galectin-1 from oxidative stress-induced apoptosis induced by H2O2, but TDG inhibited this antioxidant protective effect of galectin-1 and reduced tube forming activity in angiogenic assays. We show for the first time that the single agent, TDG, concurrently prevents many tumor promoting effects of galectin-1 on angiogenesis, immune dysregulation and protection against oxidative stress, providing a potent and novel small molecule as an anti-cancer drug. Electronic supplementary material The online version of this article (doi:10.1007/s10456-011-9213-5) contains supplementary material, which is available to authorized users.
    Angiogenesis 04/2011; 14(3):293-307. DOI:10.1007/s10456-011-9213-5 · 4.88 Impact Factor
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