title: COX-2 promotes metastasis in nasopharyngeal carcinoma by mediating interactions between cancer cells and myeloid-derived suppressor cells.
abstract: The expansion of myeloid-derived suppressor cells (MDSCs) is a common feature of cancer, but its biological roles and molecular mechanism remain unclear. Here, we investigated a molecular link between MDSC expansion and tumor cell metastasis in nasopharyngeal carcinoma (NPC). We demonstrated that MDSCs expanded and were positively correlated with the elevated tumorCOX-2expression and serum IL-6 levels in NPC patients. Importantly,COX-2and MDSCs were poor predictors of patient disease-free survival (DFS). Knocking down tumorCOX-2expression hampered functional TW03-mediated-MDSC cell (T-MDSC) induction with IL-6 blocking. We identified that T-MDSCs promoted NPC cell migration and invasion by triggering the epithelial-mesenchymal transition (EMT) on cell-to-cell contact, and T-MDSCs enhanced tumor experimental lung metastasisin vivo. Interestingly, the contact between T-MDSCs and NPC cells enhanced tumorCOX-2expression, which subsequently activated theβ-catenin/TCF4pathway, resulting in EMT of the cancer cells. Blocking transforming growth factor β (TGFβ) or inducible nitric oxide synthase (iNOS) significantly abolished the T-MDSC-induced upregulation ofCOX-2and EMT scores in NPC cells, whereas the administration of TGFβ or L-arginine supplements upregulatedCOX-2expression and EMT scores in NPC cells. These findings reveal thatCOX-2is a key factor mediating the interaction between MDSCs and tumor cells, suggesting that the inhibition ofCOX-2or MDSCs has the potential to suppress NPC metastasis.
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China ; Department of Biotherapy; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China.
authors.forename: Ze-Lei
authors.initials: ZL
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China ; Department of Biotherapy; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China.
authors.forename: Shu-Biao
authors.initials: SB
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China ; Department of Biotherapy; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China.
authors.forename: Li-Yin
authors.initials: LY
authors.lastname: OuYang
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China ; Department of Biotherapy; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China.
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China ; Department of Radiotherapy; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China.
authors.forename: Yu-Shan
authors.initials: YS
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China ; Department of Biotherapy; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China.
authors.forename: Jia
authors.initials: J
authors.lastname: He
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China ; Department of Nasopharyngeal Carcinoma; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China.
authors.forename: Qiu-Yan
authors.initials: QY
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China ; Department of Nasopharyngeal Carcinoma; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China.
authors.forename: Chao-Nan
authors.initials: CN
authors.lastname: Qian
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China ; Department of Biotherapy; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China.
authors.forename: Xiao-Shi
authors.initials: XS
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education; State Key Laboratory of Biocontrol; College of Life Sciences; Sun Yat-sen University ; Guangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China ; Department of Biotherapy; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
keywords: COX-2; myeloid-derived suppressor cells; nasopharyngeal carcinoma