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

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.
Mesh Terms:
Adolescent, Adult, Aged, Animals, Apoptosis, Blotting, Western, Carcinogens, Case-Control Studies, Cell Movement, Cell Proliferation, Clusterin, Female, Humans, Immunoenzyme Techniques, Immunoprecipitation, Liver Neoplasms, Lung Neoplasms, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Middle Aged, Nasopharyngeal Neoplasms, Neoplasm Invasiveness, Nitrosamines, RNA, Messenger, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Tumor Cells, Cultured, Vascular Endothelial Growth Factor A, Xenograft Model Antitumor Assays, Young Adult
Oncotarget
Date: Feb. 02, 2016
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