biostudies-literatureUnknown7(15)Yang WWSalivary 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 <i>in vivo</i>. Therefore, epiregulin, as well as epiregulin-containing exosomes, may be a novel target for controlling SACC lung metastasis.Theranostics3700-3714https://www.ebi.ac.uk/biostudies/studies/S-EPMC5667342biostudies-literatureEpiregulin Promotes Lung Metastasis of Salivary Adenoid Cystic Carcinoma.PMC5667342Yang WWXu LHLi SLGe XYFu JZhao FYang LQChen CWfalseEpiregulin Promotes Lung Metastasis of Salivary Adenoid Cystic Carcinoma.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 <i>in vivo</i>. Therefore, epiregulin, as well as epiregulin-containing exosomes, may be a novel target for controlling SACC lung metastasis.2017-01-01T00:00:00Z20172025-04-27T03:52:15.571Z2019-03-27T03:00:41ZS-EPMC56673422910977010.7150/thno.19712