Extracellular Galectin-3 in Tumor Progression and Metastasis

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.

Galectin-3 Knockdown Impairs Survival, Migration, and Immunomodulatory Actions of Mesenchymal Stromal Cells in a Mouse Model of Chagas Disease Cardiomyopathy

“…Adhesion, proliferation, and migration are processes that are consistently favored by Gal-3 expression in different cell types, and increased Gal-3 expression play a role in migration and invasion by neoplastic cells [28]. In the present study, we showed that Gal-3 knockdown in MSC was associated with decreased migration and proliferative capacity.…”

Galectin-3- Mediated Transdifferentiation of Pulmonary Artery Endothelial Cells Contributes to Hypoxic Pulmonary Vascular Remodeling

“…In recent years, Gal-3 was found to promote angiogenesis and tumor growth [15,17]. Inhibition of Gal-3 reduced atherosclerosis in apolipoprotein E-deficient mice [18].…”

The emerging roles of exosomes in leukemogeneis

“…Galectin-3 functions as a modulator of cell-cell adhesion, cell-matrix interactions, tumor angiogenesis and metastasis, immune response and apoptosis [52, 53]. Although contradictory results being reported, in general, the expression of galectin-3 is significantly higher in multiple tumors and is an indicator of metastatic potential [54].…”