The role of galectin-3 in malignant melanoma

Abstract

Mechanisms by which Galectin-3 participate in regulation of innate and acquired immune responses include adhesion of neutrophils, chemoattraction of monocytes/macrophages and activation of mast cells and T-cell survival. We have demonstrated proinflammatory effects of Galectin-3 in several experimental models of T-cell-mediated inflammatory and autoimmune diseases. Galectin-3 is also expressed in malignant cells and is involved in tumor development and progression as well as tumor immune escape. Using Galectin-3-deficient mice and malignant melanoma model we recently showed that the expression of Galectin-3 in the host cells facilitate establishment of metastasis in the lung. Mechanisms contributing to resistance to melanoma in Galectin-3-deficient mice appear to be the lower tumor cell adhesion and modulation of immune responses. Galectin-3-deficient mice had higher serum levels of IFN-gamma and IL-17 and a decrease in the percentage and total number of regulatory CD4 +Foxp3+T cells compared to wild-type mice. Protective effects of Galectin-3 deficiency on metastatic melanoma spread was dependent on NK cells and associated with an enhanced cytotoxic activity of splenic NK cells in vitro and increased frequency of effective cytotoxic CD27 highCD11bhigh NK cells as well as immature CD27 highCD11blowNK cells in vivo. Thus, target inhibition of Galectin-3 expression can prevent melanoma metastasis by decreasing tumor cell adhesion and by enhancing NK cell-mediated anti-tumor immune response. © 2012 American Chemical Society.