Theranostics 2017; 7(15):3700-3714. doi:10.7150/thno.19712 This issue Cite

Research Paper

Epiregulin Promotes Lung Metastasis of Salivary Adenoid Cystic Carcinoma

Wen-Wen Yang1, Lin-Qian Yang1, Fei Zhao1, Chu-Wen Chen1, Li-Hua Xu1, Jia Fu2, Sheng-Lin Li1,2✉, Xi-Yuan Ge1,2✉

1. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, PR China;
2. Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, PR China.

Citation:
Yang WW, Yang LQ, Zhao F, Chen CW, Xu LH, Fu J, Li SL, Ge XY. Epiregulin Promotes Lung Metastasis of Salivary Adenoid Cystic Carcinoma. Theranostics 2017; 7(15):3700-3714. doi:10.7150/thno.19712. https://www.thno.org/v07p3700.htm
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Abstract

Graphic abstract

Salivary adenoid cystic carcinoma (SACC) is a peculiar malignant tumor, characterized by its slow but inexorable growth, with a high incidence of lung metastasis and poor prognosis. Here, we show the upregulated expression of EGFR ligand epiregulin in a subset of SACC cells correlates with lung metastasis and unfavorable outcome in patients with SACC. We found that upregulation of epiregulin in SACC cells induced epithelial-mesenchymal transition by regulating GLI1/E-cadherin. Elevated epiregulin increased the expression of pro-angiogenic factors, such as VEGFA, bFGF, and IL-8. We also show that epiregulin can be delivered via exosomes and was enriched in exosomes derived from epiregulin-overexpressing SACC cells. Furthermore, treating immunodeficient mice with these epiregulin-enriched exosomes greatly enhanced SACC metastasis to lung. These epiregulin-enriched exosomes significantly enhanced angiogenesis in the neighboring tumor microenvironment and increased vascular permeability in the pre-metastatic lung microenvironment in vivo. Therefore, epiregulin, as well as epiregulin-containing exosomes, may be a novel target for controlling SACC lung metastasis.

Keywords: adenoid cystic cacinoma, epiregulin, lung metastasis, exosomes, pre-metastatic niche


Citation styles

APA
Yang, W.W., Yang, L.Q., Zhao, F., Chen, C.W., Xu, L.H., Fu, J., Li, S.L., Ge, X.Y. (2017). Epiregulin Promotes Lung Metastasis of Salivary Adenoid Cystic Carcinoma. Theranostics, 7(15), 3700-3714. https://doi.org/10.7150/thno.19712.

ACS
Yang, W.W.; Yang, L.Q.; Zhao, F.; Chen, C.W.; Xu, L.H.; Fu, J.; Li, S.L.; Ge, X.Y. Epiregulin Promotes Lung Metastasis of Salivary Adenoid Cystic Carcinoma. Theranostics 2017, 7 (15), 3700-3714. DOI: 10.7150/thno.19712.

NLM
Yang WW, Yang LQ, Zhao F, Chen CW, Xu LH, Fu J, Li SL, Ge XY. Epiregulin Promotes Lung Metastasis of Salivary Adenoid Cystic Carcinoma. Theranostics 2017; 7(15):3700-3714. doi:10.7150/thno.19712. https://www.thno.org/v07p3700.htm

CSE
Yang WW, Yang LQ, Zhao F, Chen CW, Xu LH, Fu J, Li SL, Ge XY. 2017. Epiregulin Promotes Lung Metastasis of Salivary Adenoid Cystic Carcinoma. Theranostics. 7(15):3700-3714.

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