Oncotarget

Research Papers:

Oleate-induced PTX3 promotes head and neck squamous cell carcinoma metastasis through the up-regulation of vimentin

Shih-Hung Chan _, Jhih-Peng Tsai, Chih-Jie Shen, Yu-Han Liao and Ben-Kuen Chen

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Oncotarget. 2017; 8:41364-41378. https://doi.org/10.18632/oncotarget.17326

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Abstract

Shih-Hung Chan1, Jhih-Peng Tsai1,2, Chih-Jie Shen2,3, Yu-Han Liao2 and Ben-Kuen Chen2,4,5,6

1Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan, People’s Republic of China

2Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan, People’s Republic of China

3Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan, People’s Republic of China

4Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan, People’s Republic of China

5Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan, People’s Republic of China

6Institute for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan, People’s Republic of China

Correspondence to:

Ben-Kuen Chen, email: bkchen58@mail.ncku.edu.tw

Keywords: oleate, PTX3, metastasis

Received: February 09, 2017     Accepted: March 30, 2017     Published: April 21, 2017

ABSTRACT

The association between metabolic diseases and the risk of developing cancer is emerging. However, the impact of long pentraxin-3 (PTX3) on dyslipidemia-associated tumor metastasis remains unknown. In this study, we found that oleate induced PTX3 expression and secretion through the activation of Akt/NF-κB pathway in head and neck squamous cell carcinomas (HNSCCs). The activation of NF-κB was essential for the oleate-induced stabilization of PTX3 mRNA. In addition, both the depletion of PTX3 and the inhibition of NF-κB significantly inhibited oleate-induced tumor cell migration and invasion. The enhancement of binding between tumor and endothelial cells was observed in oleate-treated cells but not in the depletion and neutralization of PTX3 with siPTX3 and anti-PTX3 antibodies, respectively. The levels of oleate-induced epithelial-mesenchymal transition (EMT) markers, such as vimentin and MMP-3, were significantly reduced in PTX3-depleted cells. Knocking down vimentin also repressed oleate-induced HNSCC invasion. Furthermore, the depletion of PTX3 blocked the oleate-primed metastatic seeding of tumor cells in the lungs. These results demonstrate that oleate enhances HNSCC metastasis through the PTX3/vimentin signaling axes. The inhibition of PTX3 could be a potential strategy for the treatment of dyslipidemia-mediated HNSCC metastasis.


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