Clusterin induced by N,N'-Dinitrosopiperazine is involved in nasopharyngeal carcinoma metastasis

// Yuejin Li 1, 2, * , Jinping Lu 2, * , Shan Zhou 2, * , Weiwei Wang 2 , Gongjun Tan 2 , Zhenlin Zhang 2 , Zigang Dong 3 , Tiebang Kang 1 , Faqing Tang 2 1 State Key Laboratory of Oncology in South China and Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong, China 2 Clinical Laboratory and Medical Research Center, Zhuhai Hospital, Jinan University, Zhuhai People’s Hospital, Zhuhai 519000, Guangdong, China 3 Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA * These authors have contributed equally to this work Correspondence to: Faqing Tang, e-mail: tangfaqing33@hotmail.com Tiebang Kang e-mail: kangtb@mail.sysu.edu.cn Keywords: N,N′-Dinitrosopiperazine, clusterin, nasopharyngeal carcinoma, metastasis Received: September 03, 2015      Accepted: December 07, 2015      Published: December 24, 2015 ABSTRACT Nasopharyngeal carcinoma (NPC) has a high metastatic clinicopathological feature. As a carcinogen factor, N,N′-Dinitrosopiperazine (DNP) is involved in NPC metastasis, but its precise mechanism has not been fully elucidated. Herein, we showed that DNP promotes NPC metastasis through up-regulating anterior clusterin (CLU). DNP was found to increase CLU, matrix metalloproteinases (MMP) 9 and vascular endothelial growth factor (VEGF) expression and activity, further DNP-increased MMP-9 and VEGF expression was through up-regulating CLU. We also found that DNP increased the binding of CLU with MMP-9 or VEGF. DNP induced the motility and invasion of NPC cell, which was inhibited by siRNA-CLU. The clinical investigation showed that CLU, MMP-9 and VEGF were positively correlated with the tumor-node -metastasis (TNM) classification. These results indicate that DNP may promote NPC tumor metastasis through up-regulating CLU, MMP-9 and VEGF expression. Therefore, DNP-increased CLU expression may be an important factor of NPC-high metastasis, and CLU may serve as a biomarker for NPC metastasis.