Galectin 3 as a guardian of the tumor microenvironment

Abstract

Galectin 3 is a member of a family of β-galactoside binding proteins and has emerged as an important regulator of diverse functions critical in cancer biology including apoptosis, metastasis, immune surveillance, molecular trafficking, mRNA splicing, gene expression, and inflammation. Galectin 3's ability to support cancer cell survival by intra-cellular and extra-cellular mechanisms suggests this molecule is an important component of the tumor microenvironment that potentially could be targeted for therapy. Data is emerging that Galectin 3 is elevated in many cancers including solid tumors and the cancers of the blood. Galectin 3 also appears to be a key molecule produced by tumor microenvironment support cells including mesenchymal stromal cells (MSC) to suppress immune surveillance by killing T cells and interfering with NK cell function and by supporting metastasis. Levels of Galectin 3 increase in the MSC of aging mice and perhaps this contributes to the development of cancer in the elderly. Galectin 3 modulates surface protein expression of a diverse set of glycoproteins including CD44 by regulating endocytosis of these proteins. In addition, Galectin 3 binding to receptor kinases such as CD45 and the T cell receptor is critical in the regulation of their function. In this review I will examine the various mechanisms how Galectin 3 supports chemoresistance and metastasis in solid tumors and in leukemia and lymphoma. I will also discuss possible therapeutic strategies to target this Galectin for cancer therapy. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza.

Activation of Human Basophils by A549 Lung Epithelial Cells Reveals a Novel IgE-Dependent Response Independent of Allergen

“…Finally, galectin-dependent activation of basophils is conceivably linked even to diseases for which basophils have only recently been implicated in, such as lupus (51) and cancer (52). This is because other reports show that galectins are widely expressed in the same tissues (53, 54). Thus, a synthesis of these findings, along with our proposed mechanism, might further explain why IL-4-producing basophils are seen in both diseases –they are triggered through an IgE/galectin interaction.…”

Galectin-3, a Druggable Vulnerability for KRAS-Addicted Cancers

“…Previous studies have shown that Galectin-3, a metastasis-inducing protein expressed by tumor cells and inflammatory cells [32–34], not only binds in a multimeric manner to the oligosaccharides on the extracellular domain of integrin αvβ3 [14], but it also associates directly or indirectly with KRAS [35], mediates KRAS clustering at the plasma membrane [36–38], and can augment KRAS activity [39, 40]. In fact, we previously reported that αvβ3 and Galectin-3 form a membrane complex with KRAS to promote tumor stemness and drug resistance [15].…”

Eviction from the sanctuary: Development of targeted therapy against cell adhesion molecules in acute lymphoblastic leukemia

“…Stromal cells are known to secrete soluble factors such as galectin-3, which are involved in imparting chemoresistance in hematological cancers (57–59) (Table 14). An example by which a secretory factor from ALL cells influences the bone marrow microenvironment and modulates it to suit its benefit is connective tissue growth factor (CTGF).…”