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Oncoimmunology. 2015 Jul 9;4(11):e1044712. eCollection 2015 Nov.

COX-2 promotes metastasis in nasopharyngeal carcinoma by mediating interactions between cancer cells and myeloid-derived suppressor cells.

Author information

1
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.
2
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.
3
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.
4
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.
5
State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Sun Yat-Sen University Cancer Center (SYSUCC) ; Guangzhou, China.

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 tumor COX-2 expression and serum IL-6 levels in NPC patients. Importantly, COX-2 and MDSCs were poor predictors of patient disease-free survival (DFS). Knocking down tumor COX-2 expression 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 metastasis in vivo. Interestingly, the contact between T-MDSCs and NPC cells enhanced tumor COX-2 expression, which subsequently activated the β-catenin/TCF4 pathway, 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 of COX-2 and EMT scores in NPC cells, whereas the administration of TGFβ or L-arginine supplements upregulated COX-2 expression and EMT scores in NPC cells. These findings reveal that COX-2 is a key factor mediating the interaction between MDSCs and tumor cells, suggesting that the inhibition of COX-2 or MDSCs has the potential to suppress NPC metastasis.

KEYWORDS:

COX-2; myeloid-derived suppressor cells; nasopharyngeal carcinoma

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