The expansion and activity of myeloid-derived suppressor cells in nasopharyngeal carcinoma mediated by up-regulating COX-2 (TUM6P.964)

Abstract

Abstract The expansion of myeloid-derived suppressor cells (MDSCs) is linked to tumor metastasis, but the molecular mechanism related to this link remains unclear. Here, we investigated the interactions between MDSCs and tumor cells in patients with nasopharyngeal carcinoma (NPC) and demonstrated that NPC cells induced the expansion of tumor-induced MDSCs (T-MDSCs); in turn T-MDSCs enhanced NPC cell migration and metastasis. Up-regulation of tumor cyclooxygenase-2 (COX-2) expression positively correlated with the expansion of MDSCs in NPC patients and both of COX-2 and MDSCs were poor predictors for disease-free survival. In vitro, knockdown of COX-2 expression in TW03 cells hampered T-MDSC induction by blocking IL-6. In addition, T-MDSCs promoted NPC cell proliferation, invasion and migration by triggering the epithelial-mesenchymal transition (EMT) on cell-to-cell contact; furthermore, T-MDSCs enhanced tumor lung metastasis in nude mice. Interestingly, T-MDSCs-mediated EMT was through enhancing COX-2 expression and activating the b-catenin/TCF4 pathway in NPC cells; Blockage of TGFb and iNOS significantly abolished the T-MDSC-mediated up-regulation of COX-2 and EMT in NPC cells, whereas the administration of TGFb and L-arginine supplements up-regulated COX2 expression and the b-catenin/TCF4 pathway in NPC cells. Taken together, these findings unveil a pivotal role for COX-2 in the development and cancerous contributions of MDSCs in NPC.