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

Abstract

// Shih-Hung Chan 1 , Jhih-Peng Tsai 1, 2 , Chih-Jie Shen 2, 3 , Yu-Han Liao 2 and Ben-Kuen Chen 2, 4, 5, 6 1 Division 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 2 Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan, People’s Republic of China 3 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan, People’s Republic of China 4 Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan, People’s Republic of China 5 Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan, People’s Republic of China 6 Institute 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.