Epiregulin Promotes Lung Metastasis of Salivary Adenoid Cystic Carcinoma.
Theranostics
; 7(15): 3700-3714, 2017.
Article
em En
| MEDLINE
| ID: mdl-29109770
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.
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Base de dados:
MEDLINE
Assunto principal:
Carcinoma Adenoide Cístico
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Epirregulina
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Neoplasias Pulmonares
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article