首页|High COX‐2 expression in cancer‐associated fibiroblasts contributes to poor survival and promotes migration and invasiveness in nasopharyngeal carcinoma

High COX‐2 expression in cancer‐associated fibiroblasts contributes to poor survival and promotes migration and invasiveness in nasopharyngeal carcinoma

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  • NSTL
  • Wiley
Abstract Nasopharyngeal carcinoma (NPC) has the highest rate of metastasis among head and neck cancers, and distant metastasis is the major reason for treatment failure. We have previously shown that high cyclooxygenase‐2 (COX‐2) expression is associated with a poor prognosis of patients with NPC and inhibits chemotherapy‐induced senescence in NPC cells. In this study, we found that COX‐2 was upregulated in cancer‐associated fibroblasts (CAFs) derived from NPC by RNA‐Seq. Furthermore, elevated COX‐2 expression in CAF was detected in NPC patients with poor survival and distant metastasis by using immunohistochemistry. Then, we identified that COX‐2 is highly expressed in CAF at the distant metastasis site in seven paired NPC patients. High expression of COX‐2 and secretion of prostaglandin E2, a major product catalyzed by COX‐2 in fibroblasts, promotes migration and invasiveness of NPC cells in vitro. On the contrary, inhibition of COX‐2 has the opposite effect in vitro as well as in the COX‐2 ?/? mouse with the lung metastasis model in vivo. Mechanistically, we discovered that COX‐2 elevates tumor necrosis factor‐α expression in CAF to promote NPC cell migration and invasiveness. Overall, our results identified a novel target in CAF promoting NPC metastasis. Our findings suggested that high expression of COX‐2 in CAF may serve as a new prognostic indicator for NPC metastasis and provide the possibility of targeting CAF for treating advanced NPC.

cancer‐associated fibroblastsCOX‐2metastasisnasopharyngeal carcinoma

Liu Guizhu、Jiang Weihong、Zhang Xin、Chen Shilian、Guo Jiaojiao、Jian Xingxing、Ouyang Jian、Xia Jiliang、Kuang Chunmei、Fan Songqing、Wu Xuan、Wu Yangbowen、Zhou Wen、Guan Yongjun、Zhu Yinghong、Shi Chen、Zeng Liang

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Key Laboratory of Nutrition and Metabolism, Institute for Nutritional SciencesChinese Academy of

Department of Otolaryngology Head and Neck Surgery, Xiangya HospitalCentral South

Shanghai Center for Bioinformation TechnologyShanghai Academy of Science and TechnologyShanghai

Department of PathologySecond Xiangya Hospital of Central South UniversityChangsha,China

Department of PathologyGuangzhou Women and Children's Medical CenterGuangzhou,China

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2020

10.1002/mc.23150

Molecular Carcinogenesis

Molecular Carcinogenesis

SCI
ISSN：0899-1987
年,卷(期)：2020.59(3)
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