Abstract
Galectins are glycan-binding proteins that contain one or two carbohydrate domains and mediate multiple biological functions. By analyzing clinical tumor samples, the abnormal expression of galectins is known to be linked to the development, progression and metastasis of cancers. Galectins also have diverse functions on different immune cells that either promote inflammation or dampen T cell-mediated immune responses, depending on cognate receptors on target cells. Thus, tumor-derived galectins can have bifunctional effects on tumor and immune cells. This review focuses on the biological effects of galectin-1, galectin-3 and galectin-9 in various cancers and discusses anticancer therapies that target these molecules.
Highlights
Galectins are a family of lectins composed of one or two carbohydrate-recognition domains (CRDs) that bind to beta-galactoside-containing glycans
Among the 11 galectins identified in humans, galectin-1, galectin-3 and galectin-9 have been the most extensively investigated in different fields including cell biology and immunology
We have summarized the roles of galectins in human cancer biology and focused on targeting the inhibition of these molecules in ongoing clinical trials
Summary
Galectins are a family of lectins composed of one or two carbohydrate-recognition domains (CRDs) that bind to beta-galactoside-containing glycans. Galectins are soluble proteins that are widely expressed in various cell types and mediate their functions both intracellularly and extracellularly. The functions of galectins include the regulation of cell growth, apoptosis, pre-mRNA splicing, cell-cell and cell-matrix adhesion, cellular polarity, motility, differentiation, transformation, signal transduction and innate/adaptive immunity. Given the preferred glycan branch of an individual galectin, each type can bind to a set of glycoconjugates on the cell surface that mediates specific functions. Galectin-1 binds to CD2, CD3, CD7, CD43 and CD45 on T cells, which downregulate immune responses by inducing apoptosis. Galectin-9 has a dual function, by binding to T cell immunoglobulin mucin 3 (TIM-3) expressed on T cells or dendritic cells, which induces apoptosis or inflammatory responses, respectively. Given the multiple immune regulatory functions of galectins on T cells, we summarize the results of clinical trials that used galectin inhibitors combined with various forms of chemotherapy or immunotherapy
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