Galectin-3 as a Potential Target to Prevent Cancer Metastasis (original) (raw)
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Galectin-3: a potential target for cancer prevention
Trends in carbohydrate research, 2011
Protein-carbohydrate interactions play significant role in modulating cell-cell and cell-extracellular matrix interactions, which, in turn, mediate various biological processes such as growth regulation, immune function, cancer metastasis, and apoptosis. Galectin-3, a member of the β-galactoside-binding protein family, is found multifunctional and is involved in normal growth development as well as cancer progression and metastasis, but the detailed mechanisms of its functions are not well understood. This review discusses its structure, binding properties, transcriptional regulation and roles in homotypic/heterotypic cell adhesion, angiogenesis and apoptosis.
Galectin-3 Binding and Metastasis
Metastasis Research Protocols
Galectin-3 is a member of a family of carbohydrate-binding proteins. It is present in the nucleus, the cytoplasm and also extracellular matrix of many normal and neoplastic cell types. Arrays of reports show an upregulation of this protein in transformed and metastatic cell lines (1, 2). Moreover, in many human carcinomas, an increased expression of galectin-3 correlates with progressive tumor stages (3-6). Several lines of analysis have demonstrated that the galectins participate in cell-cell and cell-matrix interactions by recognizing and binding complimentary glycoconjugates and thereby play a crucial role in normal and pathological processes. Elevated expression of the protein is associated with an increased capacity for anchorage-independent growth, homotypic aggregation, and tumor cell lung colonization (7-9). In this chapter we describe the methods of purification of galectin-3 from transformed E. coli and some of the commonly used functional assays for analyzing galectin-3 binding.
Role of Galectin-3 in Cancer Metastasis
Glycobiology Insights, 2015
Galectins are a family of proteins that contain a canonical carbohydrate-recognition domain (CRD) with affinity for beta-galactosides. Within this family, an unique member, the chimeric, galectin-3, may be found in the cytoplasm and nucleus, and on the cell surface, besides being released into the extracellular space. Galectin-3 interactions with certain glycans and extracellular matrix (ECM) proteins have been described to promote and/ or antagonize tumor cell apoptosis, to induce endothelial cell proliferation and angiogenesis, and to promote tumor cell adhesion and invasion, thus both potentially facilitating and hindering metastasis. Moreover, although galectin-3 is expressed in several types of malignancies and its expression has been correlated with transformation and metastasis-related events, its downregulation has also been associated with malignancy and tumor progression. These apparently conflicting data demonstrate that the role of galectin-3 in metastasis remains to be fully understood. Of course in nature, different cancer progression phenomena are simultaneously occurring in the many instances, where the patient has primary tumor and blood-borne and distant metastatic cells. This makes it all the more interesting to overview the role of galectins in cancer metastasis, especially galectin-3, since these and their related molecules are more than probable disease marker candidates and/or therapeutic targets.
Glycoconjugate Journal, 2000
Galectin-3, a 31 kDa member of the β-galactoside-binding proteins, is an intracellular and extracellular lectin which interacts with intracellular glycoproteins, cell surface molecules and extracellular matrix proteins. Galectin-3 is expressed widely in epithelial and immune cells and its expression is correlated with cancer aggressiveness and metastasis. Galectin-3 is involved in various biological phenomena including cell growth, adhesion, differentiation, angiogenesis and apoptosis. Recent research revealed that galectin-3 is associated with several steps of invasion and metastasis, like angiogenesis, cell-matrix interaction, dissemination through blood flow and extravasation. Recently, we and others have shown that galectin-3 can be a reliable diagnostic marker in certain cancers and one of the target proteins of cancer treatment. In this review, we describe the involvement of galectin-3 in each steps of metastasis and clinical significance of galectin-3. Published in 2004.
Role of galectin 3 binding protein in cancer progression: a potential novel therapeutic target
Journal of Translational Medicine
The lectin galactoside-binding soluble 3 binding protein (LGALS3BP) is a secreted, hyperglycosylated protein expressed by the majority of human cells. It was first identified as cancer and metastasis associated protein, while its role in innate immune response upon viral infection remains still to be clarified. Since its discovery dated in early 90 s, a large body of literature has been accumulating highlighting both a prognostic and functional role for LGALS3BP in cancer. Moreover, data from our group and other have strongly suggested that this protein is enriched in cancer-associated extracellular vesicles and may be considered a promising candidate for a targeted therapy in LGALS3BP positive cancers. Here, we extensively reviewed the literature relative to LGALS3BP role in cancer and its potential value as a therapeutic target.
Cancer research, 1995
Galectin-1 and galectin-3, galactoside-binding lectins with molecular weights of M(r) 14,500 and 31,000, respectively, are expressed in normal and malignant cells and have been implicated in regulation of cell growth, adhesion, and metastasis. We analyzed the expression of galectins in 21 cultured human colon carcinoma cell lines by immunoblotting. Galectin-1 was detected in only 7, whereas galectin-3 was found in 20 of the cell lines. KM12 cells, which express only galectin-3, were used to isolate this lectin by affinity chromatography, and the purified lectin was used to identify complementary glycoconjugates by blotting. Galectin-3 was shown to bind to human laminin, carcinoembryonic antigen, and lysosome-associated membrane glycoproteins, which are involved in cell adhesion. Galectin-3 was localized on the KM12 cell surface and colocalized with carcinoembryonic antigen. Several endogenous glycoproteins and cell surface proteins of molecular weights in the range M(r) 58,000 to &g...
Galectin-3: A factotum in carcinogenesis bestowing an archery for prevention
Tumor Biology
Cancer metastasis and therapy resistance are the foremost hurdles in oncology at the moment. This review aims to pinpoint the functional aspects of a unique multifaceted glycosylated molecule in both intracellular and extracellular compartments of a cell namely galectin-3 along with its metastatic potential in different types of cancer. All materials reviewed here were collected through the search engines PubMed, Scopus, and Google scholar. Among the 15 galectins identified, the chimeric gal-3 plays an indispensable role in the differentiation, transformation, and multi-step process of tumor metastasis. It has been implicated in the molecular mechanisms that allow the cancer cells to survive in the intravascular milieu and promote tumor cell extravasation, ultimately leading to metastasis. Gal-3 has also been found to have a pivotal role in immune surveillance and pro-angiogenesis and several studies have pointed out the importance of gal-3 in establishing a resistant phenotype, par...
Galectins–potential targets for cancer therapy
Cancer letters, 2007
Galectins are a family of galactose binding lectins that have become the focus of attention of cancer biologists due to their numerous regulatory roles in normal cellular metabolism and also because of their altered levels in various cancers. They are reportedly similar to several prominent and established modulators of apoptosis. In this review, we present a brief outline of the advancements in the methodology used to detect and identify them and their therapeutic applications in cancer. Their possible interactions with other glycoconjugates are also discussed and a vision for their future use in diagnosis and therapeutics is provided.
Galectin-3: An open-ended story
Galectins, an ancient lectin family, are characterized by specific binding of β-galactosides through evolutionary conserved sequence elements of carbohydrate-recognition domain (CRD). A structurally unique member of the family is galectin-3; in addition to the CRD it contains a prolineand glycine-rich N-terminal domain (ND) through which is able to form oligomers. Galectin-3 is widely spread among different types of cells and tissues, found intracellularly in nucleus and cytoplasm or secreted via non-classical pathway outside of cell, thus being found on the cell surface or in the extracellular space. Through specific interactions with a variety of intra-and extracellular proteins galectin-3 affects numerous biological processes and seems to be involved in different physiological and pathophysiological conditions, such as development, immune reactions, and neoplastic transformation and metastasis. The review attempts to summarize the existing information on structural, biochemical and intriguing functional properties of galectin-3.
Journal of Oncology, 2019
Galectin-3 (Gal-3) is a multifunctionalβ-galactoside-binding lectin that once synthesized is expressed in the nucleus, cytoplasm, cell surface, and extracellular environment. Gal-3 plays an important role in breast cancer tumors due to its ability to promote interactions between cell-cell and cell-extracellular matrix (ECM) elements, increasing tumor survival and metastatic dissemination. Still, the mechanism by which Gal-3 interferes with tumor cell migration and metastasis formation is complex and not fully understood. Here, we showed that Gal-3 knockdown increased the migration ability of 4T1 murine breast cancer cellsin vitro. Using the 4T1 orthotopic breast cancer spontaneous metastasis mouse model, we demonstrated that 4T1-derived tumors were significantly larger in the presence of Gal-3 (scramble) in comparison with Gal-3 knockdown 4T1-derived tumors. Nevertheless, Gal-3 knockdown 4T1 cells were outnumbered in the bone marrow in comparison with scramble 4T1 cells. Finally, we...