Abstract
Galectin-3, the only chimera galectin found in vertebrates, is one of the best-studied galectins. It is expressed in several cell types and is involved in a broad range of physiological and pathological processes, such as cell adhesion, cell activation and chemoattraction, cell cycle, apoptosis, and cell growth and differentiation. However, this molecule raises special interest due to its role in regulating cancer cell activities. Galectin-3 has high affinity for β-1,6-N-acetylglucosamine branched glycans, which are formed by the action of the β1,6-N-acetylglucosaminyltransferase V (Mgat5). Mgat5-related changes in protein/lipid glycosylation on cell surface lead to alterations in the clustering of membrane proteins through lattice formation, resulting in functional advantages for tumor cells. Galectin-3 presence enhances migration and/or invasion of many tumors. Galectin-3-dependent clustering of integrins promotes ligand-induced integrin activation, leading to cell motility. Galectin-3 binding to mucin-1 increases transendothelial invasion, decreasing metastasis-free survival in an experimental metastasis model. Galectin-3 also affects endothelial cell behavior by regulating capillary tube formation. This lectin is found in the tumor stroma, suggesting a role for microenvironmental galectin-3 in tumor progression. Galectin-3 also seems to be involved in the recruitment of tumor-associated macrophages, possibly contributing to angiogenesis and tumor growth. This lectin can be a relevant factor in turning bone marrow in a sanctuary for leukemia cells, favoring resistance to therapy. Finally, galectin-3 seems to play a relevant role in orchestrating distinct cell events in tumor microenvironment and for this reason, it can be considered a target in tumor therapies. In conclusion, this review aims to describe the processes of tumor progression and metastasis involving extracellular galectin-3 and its expression and regulation.
Highlights
Galectins comprise a family of animal lectins defined by their ability to recognize β-galactoside-containing glycoconjugates through a conserved carbohydrate-recognition domain (CRD)
We aim to examine recent data regarding the extracellular functions of galectin-3 in some steps of tumor progression and metastasis
Galectin-3 has been explored as a target for cancer therapy
Summary
Galectins comprise a family of animal lectins defined by their ability to recognize β-galactoside-containing glycoconjugates through a conserved carbohydrate-recognition domain (CRD). While prototype galectins are usually homodimers with two polypeptides containing a CRD each, tandem repeat galectins are monomers presenting two CRDs, connected by a linker region. In turn, consist of one CRD connected to a collagen-like sequence formed by Pro-Gly-Tyr tandem repeats and an N-terminal domain (Figure 1A). Galectins are involved in physiological and pathological events, such as cell proliferation and differentiation, apoptosis, immune response, cell differentiation, and tumor progression. The mechanisms underlying these aspects are currently under massive investigation
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