title: Clusterin induced by N,N'-Dinitrosopiperazine is involved in nasopharyngeal carcinoma metastasis.
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.
authors.affiliation: State Key Laboratory of Oncology in South China and Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong, China.|Clinical Laboratory and Medical Research Center, Zhuhai Hospital, Jinan University, Zhuhai People's Hospital, Zhuhai 519000, Guangdong, China.
authors.forename: Yuejin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Clinical Laboratory and Medical Research Center, Zhuhai Hospital, Jinan University, Zhuhai People's Hospital, Zhuhai 519000, Guangdong, China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Lu
authors.affiliation: Clinical Laboratory and Medical Research Center, Zhuhai Hospital, Jinan University, Zhuhai People's Hospital, Zhuhai 519000, Guangdong, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Clinical Laboratory and Medical Research Center, Zhuhai Hospital, Jinan University, Zhuhai People's Hospital, Zhuhai 519000, Guangdong, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Clinical Laboratory and Medical Research Center, Zhuhai Hospital, Jinan University, Zhuhai People's Hospital, Zhuhai 519000, Guangdong, China.
authors.forename: Gongjun
authors.initials: G
authors.lastname: Tan
authors.affiliation: Clinical Laboratory and Medical Research Center, Zhuhai Hospital, Jinan University, Zhuhai People's Hospital, Zhuhai 519000, Guangdong, China.
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Oncology in South China and Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong, China.
authors.forename: Tiebang
authors.initials: T
authors.lastname: Kang
authors.affiliation: Clinical Laboratory and Medical Research Center, Zhuhai Hospital, Jinan University, Zhuhai People's Hospital, Zhuhai 519000, Guangdong, China.
authors.forename: Faqing
authors.initials: F
authors.lastname: Tang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002273:Carcinogens / Q000494:pharmacology; D002277:Carcinoma; D016022:Case-Control Studies; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D051152:Clusterin / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D008113:Liver Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000556:secondary*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000556:secondary*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009602:Nitrosamines / Q000009:adverse effects*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult
chemical_list: C495242:CLU protein, human; D002273:Carcinogens; D051152:Clusterin; D009602:Nitrosamines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C026156:N,N'-dinitrosopiperazine
keywords: N,N′-Dinitrosopiperazine; clusterin; metastasis; nasopharyngeal carcinoma