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

Oncotarget. 2016 Feb 2;7(5):5548-63. doi: 10.18632/oncotarget.6750.

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.

Keywords: N,N′-Dinitrosopiperazine; clusterin; metastasis; nasopharyngeal carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Apoptosis / drug effects
  • Blotting, Western
  • Carcinogens / pharmacology
  • Carcinoma
  • Case-Control Studies
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Clusterin / genetics
  • Clusterin / metabolism*
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Immunoprecipitation
  • Liver Neoplasms / chemically induced
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary*
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / chemically induced
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology*
  • Neoplasm Invasiveness
  • Nitrosamines / adverse effects*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Xenograft Model Antitumor Assays
  • Young Adult

Substances

  • CLU protein, human
  • Carcinogens
  • Clusterin
  • Nitrosamines
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • N,N'-dinitrosopiperazine