Galectin

About: Galectin is a research topic. Over the lifetime, 2076 publications have been published within this topic receiving 103409 citations. The topic is also known as: IPR001079 & Galectin.

Aberrant Glycosylation Promotes Lung Cancer Metastasis through Adhesion to Galectins in the Metastatic Niche

Abstract: Metastasis is the leading cause of cancer-associated deaths. While dissemination of tumor cells likely occurs early in tumorigenesis, the constituents of the microenvironment play essential rate-limiting roles in determining whether these cells will form clinically-relevant tumors. Recent studies have uncovered many molecular factors that contribute to establishment of a pro-tumorigenic metastatic niche. Here, we demonstrate that galectin-3, whose expression has clinical associations with advanced malignancy and poor outcome, contributes to metastatic niche formation by binding to carbohydrates on metastatic cells. We show that galectin-3 is expressed early during tumorigenesis by both CD11b+Gr-1+ and CD11b+Ly-6Chi leukocytes. Tumors mobilize these myeloid populations through secretion of soluble factors including IL-6. We find that metastatic cancer cells exhibit elevated presentation of the oncofetal galectin-3 carbohydrate ligand, the Thomsen-Friedenreich Antigen, on their surfaces as a result of altered C2GnT2 and St6GalNAcIV glycosyltransferase activity that inhibits further glycosylation of this carbohydrate motif and promotes metastasis.

Design and synthesis of novel 3-triazolyl-1-thiogalactosides as galectin-1, -3 and -8 inhibitors

Abstract: Galectins are galactoside-binding proteins that play a role in various pathophysiological conditions, making them attractive targets in drug discovery. We have designed and synthesised a focused library of aromatic 3-triazolyl-1-thiogalactosides targeting their core site for binding of galactose and a subsite on its non-reducing side. Evaluation of their binding affinities for galectin-1, -3, and -8N identified acetamide-based compound 36 as a suitable compound for further affinity enhancement by adding groups at the reducing side of the galactose. Synthesis of its dichlorothiophenyl analogue 59 and the thiodigalactoside analogue 62 yielded promising pan-galectin inhibitors.

Galectin binding proteins in serum and bronchoalveolar lavage -in healthy and pathological conditions

Abstract: Galectins are carbohydrate binding proteins, implicated in conditions of both inflammation and cancer. Connections between chronic inflammation and cancer are proposed by the increased remodelling and proliferation that occurs, leading to enhanced survival and proliferation of malignant cells. Since galectins have been implicated in mechanisms of both chronic inflammation and cancer, we have investigated natural binding partners of galectins in healthy individuals and then continued with studying states of cancer and chronic inflammation. We identified galectin binding glycoproteins in sera from healthy individuals and found that galectins widely expressed in the body bind serum glycoproteins well, whereas galectins with a more tissue-specific distribution scarcely binds any serum glycoproteins. We then chose the widely expressed but intermediately binding galectin-1 to detect if levels of galectin-1-binding proteins are increased in sera of breast cancer patients. We found that galectin-1 binds approximately double the amount in breast cancer patients compared to healthy individuals. The increase was mainly caused by haptoglobin, probably due to both increased expression and changes of glycosylation. To further investigate the inflammatory connection we identified galectin binding proteins from bronchoalveolar lavage of asthma patients and healthy individuals, additionally we compared the binding of galectin-3 and galectin-8 that are expressed in different sites of the lung. We found when functionally grouping the bound proteins that galectin-3 and -8 binding proteins had different profiles and that bound proteins of healthy and asthma patients differed. (Less)