Abstract
Secreted animal lectins of the galectin family are key players in cancer growth and metastasis. Here we show that galectin-8 (gal-8) induces the expression and secretion of cytokines and chemokines such as SDF-1 and MCP-1 in a number of cell types. This involves gal-8 binding to a uPAR/LRP1/integrin complex that activates JNK and the NFkB pathway. Cytokine and chemokine secretion, induced by gal-8, promotes migration of cancer cells toward cells treated with this lectin. Indeed, immune-competent gal-8 knockout (KO) mice express systemic lower levels of cytokines and chemokines while the opposite is true for gal-8 transgenic animals. Accordingly, gal-8 KO mice experience reduced tumor size and smaller and fewer metastatic lesions when injected with cancer cells. These results suggest the existence of a 'vicious cycle' whereby gal-8 secreted by the tumor microenvironment, promotes secretion of chemoattractants at the metastatic niche that promote further recruitment of tumor cells to that site. This study further implicate gal-8 in control of cancer progression and metastasis through its effects on the production of immunoregulatory cytokines.