Histidine decarboxylase-expressing PMN-MDSC-derived TGF-ß1 promotes the epithelial-mesenchymal transition of metastatic lung adenocarcinoma.
Int J Clin Exp Pathol
; 13(6): 1361-1371, 2020.
Article
em En
| MEDLINE
| ID: mdl-32661471
ABSTRACT
Metastasis is a major risk for lung adenocarcinoma-related mortality. Accumulating evidence raises the possibility that anticancer therapies might be more sensitive by targeting premetastatic niches in addition to the cancer cells themselves. Here, we identified a subpopulation of metastatic lung adenocarcinoma, which was characterized by EMT-related markers such as E-cadherin, Twist, SMAD, and ß-catenin. EMT+ cases exhibited poorer prognosis than EMT- patients, reflecting the pro-metastatic features of EMT. Immunohistochemical staining decorated CD15+ PMN-MDSCs surrounding EMT+ cancer cells in lymph nodes. Metastatic tissues secreted high levels of chemokines, including CXCL1, CXCL5, and CCL2, into the circulation to recruit histidine decarboxylase (Hdc)-positive PMN-MDSCs into metastatic colonies through upregulated CXCR2. The percentage of Hdc+ PMN-MDSCs increased in the setting of metastasis. Hdc+ PMN-MDSCs obtained from EMT+ metastatic masses expressed a higher level of TGF-ß1, rather than TGF-ß2 and TGF-ß3, compared to EMT- counterparts. The depletion of Hdc+ PMN-MDSCs or downregulation of TGF-ß1 significantly decreased EMT+ percentage and, thus, hampered the metastasis process in murine models. Together, our findings suggest that metastatic tumor secretes high levels of chemokines to recruit Hdc+ PMN-MDSCs, which, in turn, express TGF-ß1 to induce cancer cells to undergo EMT at metastatic sites.
Texto completo:
1
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Int J Clin Exp Pathol
Assunto da revista:
PATOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China