Abstract 4990: Epidermal growth factor-induced expression of PTX3 regulates metastasis of head and neck squamous cell carcinoma

Abstract

Abstract Overexpression of epidermal growth factor receptor (EGFR) and production of proinflammatroy cytokines are common in head and neck squamous cell carcinoma (HNSCC) and correlates with enhanced invasion and metastasis. However, molecular mechanisms associated with activation of EGFR and productions of cytokines in regulating metastasis of HNSCC remain poorly understood. Here, we identified PTX3 as a metastasis-promoting factor in HNSCC to regulate EGF-induced metastasis. We found that EGF induced the expression of PTX3, and was mediated through transcriptional activation, but not through mRNA stability. The involvement of Akt/NF-κB and AP-1 signaling pathways in the EGF-induced PTX3 gene expression was confirmed by knockdown of RelA and c-Jun, respectively. The expression of dominant negative IκB also repressed the activation of NF-κB and inhibited EGF-induced PTX3 expression. Furthermore, EGF increased the binding of NF-κB and c-Jun to the AP-1 binding site of the PTX3 promoter through the activation of the Akt/NF-κB pathway, which resulted in activating PTX3 promoter activity. In addition, EGF stimulated the secretion of PTX3 from cancer cells, resulting in enhancing cancer metastasis and the interaction between cancer cells and endothelial cells. EGF-enhanced metastasis-related molecules, such as fibronectin and MMP-9, and reduction of E-cadherin were reversed in PTX3 knockdown cells. These findings suggest that autocrine production of EGF-induced PTX3 regulates metastasis of HNSCC by mediating the expression levels of metastatic molecules fibronectin, MMP-9 and E-cadherin. The EGF-induced PTX3 could be a potential diagnostic marker and target for metastasis in the cancer therapy. Citation Format: Ben-Kuen Chen, Shuo-Lun Wu, Jhih-Peng Tsai. Epidermal growth factor-induced expression of PTX3 regulates metastasis of head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4990. doi:10.1158/1538-7445.AM2014-4990