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.
Glycosaminoglycans with unique sulfation patterns have been identified in different species of ascidians (sea squirts), a group of marine invertebrates of the Phylum Chordata, sub-phylum Tunicata (or Urochordata). Oversulfated dermatan sulfate composed of [4-α-L-IdoA-(2-O-SO) → 3-β-D-GalNAc(4-OSO)] repeating disaccharide units is found in the extracellular matrix of several organs, where it seems to interact with collagen fibers. This dermatan sulfate co-localizes with a decorin-like protein, as indicated by immunohistochemical analysis. Low sulfated heparin/heparan sulfate-like glycans composed mainly of [4-α-L-IdoA-(2-OSO) → 4-α-D-GlcN(SO) (6-O-SO)] and [4-α-L-IdoA-(2-O-SO) → 4-α-D-GlcN(SO)] have also been described in ascidians. These heparin-like glycans occur in intracellular granules of oocyte assessory cells, named test cells, in circulating basophil-like cells in the hemolymph, and at the basement membrane of different ascidian organs. In this review, we present an overview of the structure, distribution, extracellular and intracellular localization of the sulfated glycosaminoglycans in different species and tissues of ascidians. Considering the phylogenetic position of the subphylum Tunicata in the phylum Chordata, a careful analysis of these data can reveal important information about how these glycans evolved from invertebrate to vertebrate animals.
Bone marrow stromal cells (BMSCs) are considered a promising tool for bone bioengineering. However, the mechanisms controlling osteoblastic commitment are still unclear. Osteogenic differentiation of BMSCs requires the activation of β-catenin signaling, classically known to be regulated by the canonical Wnt pathway. However, BMSCs treatment with canonical Wnts in vitro does not always result in osteogenic differentiation and evidence indicates that a more complex signaling pathway, involving cadherins, would be required to induce β-catenin signaling in these cells. Here we showed that Wnt3a alone did not induce TCF activation in BMSCs, maintaining the cells at a proliferative state. On the other hand, we verified that, upon BMSCs osteoinduction with dexamethasone, cadherins were cleaved by the PS1/γ-secretase complex at the plasma membrane, and this event was associated with an enhanced β-catenin translocation to the nucleus and signaling. When PS1/γ-secretase activity was inhibited, the osteogenic process was impaired. Altogether, we provide evidence that PS1/γ-secretase-mediated cadherin cleavage has as an important role in controlling β-catenin signaling during the onset of BMSCs osteogenic differentiation, as part of a complex signaling pathway responsible for cell fate decision. A comprehensive map of these pathways might contribute to the development of strategies to improve bone repair.
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