Oncotarget

Research Papers:

PTX3 gene activation in EGF-induced head and neck cancer cell metastasis

Wei-Chiao Chang, Shuo-Lun Wu, Wan-Chen Huang, Jinn-Yuan Hsu, Shih-Hung Chan, Ju-Ming Wang, Jhih-Peng Tsai and Ben-Kuen Chen _

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Oncotarget. 2015; 6:7741-7757. https://doi.org/10.18632/oncotarget.3482

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Abstract

Wei-Chiao Chang1,6,7,8,9,*, Shuo-Lun Wu2,*, Wan-Chen Huang2, Jinn-Yuan Hsu3, Shih-Hung Chan4, Ju-Ming Wang2, Jhih-Peng Tsai2 and Ben-Kuen Chen2,5

1 Department of Clinical Pharmacy, Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan, ROC

2 Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan, ROC

3 Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC

4 Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC

5 Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC

6 Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC

7 Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taipei, Taiwan, ROC

8 Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC

9 Institute for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan, ROC

* These authors contributed equally to this work

Correspondence to:

Ben-Kuen Chen, email:

Keywords: PTX3, EGF, cancer metastasis

Received: November 04, 2014 Accepted: February 04, 2015 Published: March 08, 2015

Abstract

Overexpression of the epidermal growth factor (EGF) receptor (EGFR) is associated with enhanced invasion and metastasis in head and neck squamous cell carcinoma (HNSCC). Long Pentraxin PTX3 is involved in immune escape in cancer cells. Here, we identified PTX3 as a promoting factor that mediates EGF-induced HNSCC metastasis. EGF-induced PTX3 transcriptional activation is via the binding of c-Jun to the activator protein (AP)-1 binding site of the PTX3 promoter. PI3K/Akt and NF-κB were essential for the PTX3 activation. EGF-induced PTX3 expression was blocked in c-Jun- and NF-κB-knockdown cells. EGF-mediated PTX3 secretion resulted in the enhancement of cell migration and invasion, and interactions between cancer and endothelial cells. The tail-vein injection animal model revealed that depletion of PTX3 decreased EGF-primed tumor cell metastatic seeding of the lungs. In addition, fibronectin, matrix metalloproteinase-9 (MMP9) and E-cadherin were essential components in EGFR/PTX3-mediated cancer metastasis. In conclusion, PI3K/Akt and NF-κB-dependent regulation of AP-1 mediates PTX3 transcriptional responses to EGF. Autocrine production of EGF-induced PTX3 in turn induces metastatic molecules, activating inflammatory cascades and metastasis.


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