Lung cancer-derived galectin-1 contributes to cancer associated fibroblast-mediated cancer progression and immune suppression through TDO2/kynurenine axis.

ABSTRACT: Communication between cancer cells and their microenvironment plays an important role in cancer development, but the precise mechanisms by which cancer-associated fibroblasts (CAF) impact anti-cancer immunity and cancer progression in lung cancer are poorly understood. Here, we report that lung fibroblasts when activated by lung cancer cells produce tryptophan metabolite kynurenine (Kyn) that inhibits dendritic cells' differentiation and induces cancer growth as well as migration. We identified TDO2 (tryptophan 2,3-dioxygenase) as the main enzyme expressed in fibroblasts capable of tryptophan metabolism. Mechanistically, condition medium of CAF or exogenous kynurenine stimulated AKT, with no lysine 1 (WNK1) and cAMP response element-bindingprotein (CREB) phosphorylation in lung cancer cell

SUBMITTER: Hsu YL 

PROVIDER: S-EPMC5053673 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature