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Galectin-1

Official Full Name
lectin, galactoside-binding, soluble, 1
Synonyms
GBP; GAL1

Cat.No. Product Name Price
CDCL184357Human Galectin-1 ORF clone(NM_002305.3)Inquriy

Galectins are members of the large carbohydrate-binding lectins that share a highly conserved carbohydrate recognition domain (CRD) which is responsible for β-galactoside binding. Recently, some galectins, specifically Gal-1, -3, and -9, have been implicated to play a role in cancer progression. Although included in the same family, these 3 galectins are different from each other in size, function and tissue distribution. Gal-1 is considered to be the "prototype" galectin that has a CRD and can form homodimers, whereas Gal-3 and -9 are part of different galectin subgroups. Although most of Gal-1 is secreted into the extracellular matrix by an unconventional pathway, independent of the endoplasmic reticulum/ Golgi route, it can also be found in the nucleus and the cytoplasm. Gal-1 is expressed in a number of tumor types including astrocytoma, melanoma, and prostate, bladder, thyroid, colon, and ovary carcinomas, and its expression correlates with tumor metastasis and aggressiveness.

The role of galectin-1 in T cell regulation

It has been suggested that galectin-1 exposure significantly promotes the differentiation of Treg cells (CD4+CD25+FoxP3+) and their suppressive functions. When activated T cells were cultured in the presence of recombinant galectin-1, the percentage of Treg cells was significantly increased. The Gal-1-null-CD4+CD25+ Treg cells were also less capable of inhibiting the proliferation of effector T cells than wild-type CD4+CD25+ Treg cells. Another study has indicated that activation of Treg cells upregulates the levels of galectin-1 production and secretion. To summarize, these findings now make it clear that galectin-1 is an important factor contributing to the control of Treg cell immunosuppressive mechanisms.

Galectin-1 expression in tumor hypoxia

The expression of galectin-1 is upregulated by the level of HIF-1α stabilization within tumors. Several studies have suggested that hypoxia-exposed cancer cells produce the higher levels of galectin-1, which correlated with their levels of HIF-1α, and those of carbonic anhydrase IX (CA IX), whose expression is a late marker of hypoxia. These studies also indicated that knocking down the expression of galectin-1 reduced hypoxia-induced invasion and migration of colorectal cancer cell lines. These data show that the increased galectin-1 by hypoxia is related to poor prognosis of cancer patients.

These findings indicate novel mechanisms for the pro-tumorigenic actions of galectin-1 in dynamically altering the tumor microenvironment (Figure 1). Generally, the picture is emerging that the sequence of events in an abnormally growing solid tumor will firstly occur as events precipitated by the onset of intratumoral hypoxia, followed by ROS production and HIF-1α stabilization. The stabilized HIF-1α induces galectin-1 expression, which will help vascular endothelial cells to create new capillaries through activating endothelial cell proliferation and migration, reinforcing cell-cell and cell-extracellular matrix and protecting them from the oxidative stress caused by increased ROS levels existing within the tumors. Meanwhile, galectin-1 is also probably to be contributing to the protection of the immature tumor region from immune attack by inducing apoptosis of activated CD4+ and CD8+ effector T cells.

Galectin-1-1-1.jpgFigure 1. Summary of galectin-1 pro-tumorigenic functions in a tumor microenvironment.

Galectin-1 and metastasis

Galectin-1 has been shown to promote the adhesion of hepatocellular carcinoma, ovarian, melanoma, and prostate cancer cells to the extracellular matrix. The recent studies have uncovered roles for CD44 and CD326 on murine colon and breast cancer cells as galectin-1 binding targets that contribute to attachment of cancer cells to extracellular matrix and endothelial cells. In addition, galectin-1 activates platelets to induce P-selectin and the membrane glycoprotein complex (GPIIb/IIIa), resulting in their aggregation. Galectin-1 on the circulating cancer cell surfaces may bind to these molecules and form platelet cancer cell complexes. The aggregated cancer cell-platelet clusters are likely arrested in capillaries at the secondary organs, and subsequently can develop into metastases. Therefore, due to its multiple roles in the metastasis process, targeting galectin-1 might provide an effective means for inhibiting the spread of cancer.

Galectin-1 as a potential therapeutic target in cancer

Galectin-1 inhibition is the subject of increasing interest in cancer therapies. Many novel compounds or pharmacological approaches which block interactions between galectin-1 and its binding partners have been evaluated. Rabinovich et al. have described that synthetic lactulose amines are potent and specific inhibitors of galectin-1 and galectin-3 carbohydrate binding. They reported that their addition prevented galectin-1-mediated homotypic aggregation of melanoma cells, inhibited endothelial cell migration, differentiation and invasion and induced apoptosis in small cell lung carcinoma cell lines. Recently, it was proposed that exogenous oligosaccharides might mimic the endogenous ligands of these lectins, acting as quenching agents of galectin’s biological functions in survival, adhesion and migration of neoplastic cells. A series of oligosaccharide derivatives (OSDs) bearing oligosaccharide fragments of natural galectin ligands have been studied as potential galectin inhibitors in several preclinical models. Iurisci et al. showed that OSDs inhibited galectin-1 binding to the glycoprotein LGalS3BP, which is involved in neoplastic progression.

References:

  1. Laderach D J, et al. A unique galectin signature in human prostate cancer progression suggests galectin-1 as a key target for treatment of advanced disease. Cancer Research, 2013, 73(1):86-96.
  2. Ito K, et al. Galectin-1 as a potent target for cancer therapy: role in the tumor microenvironment. Cancer and Metastasis Reviews, 2012, 31(3-4):763-778.
  3. Mathieu V, et al. Galectin-1 in Melanoma Biology and Related Neo-Angiogenesis Processes. Journal of Investigative Dermatology, 2012, 132(9):2245.
  4. Cedenolaurent F, Dimitroff C J. Galectin-1 research in T cell immunity: Past, present and future. Clinical Immunology, 2012, 142(2):107-116.
  5. Banh A, et al. Tumor galectin-1 mediates tumor growth and metastasis through regulation of T-cell apoptosis. Cancer Research, 2011, 71(13):4423-4431.
  6. Astorguesxerri L, et al. Unraveling galectin-1 as a novel therapeutic target for cancer. Cancer Treatment Reviews, 2014, 40(2):307-319.

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