Particulate matter promotes cancer metastasis through increased HBEGF expression in macrophages.
Exp Mol Med
; 54(11): 1901-1912, 2022 11.
Article
en En
| MEDLINE
| ID: mdl-36352257
ABSTRACT
Although many cohort studies have reported that long-term exposure to particulate matter (PM) can cause lung cancer, the molecular mechanisms underlying the PM-induced increase in cancer metastasis remain unclear. To determine whether PM contributes to cancer metastasis, cancer cells were cultured with conditioned medium from PM-treated THP1 cells, and the migration ability of the treated cancer cells was assessed. The key molecules involved were identified using RNA-seq analysis. In addition, metastatic ability was analyzed in vivo by injection of cancer cells into the tail vein and intratracheal injection of PM into the lungs of C57BL/6 mice. We found that PM enhances the expression of heparin-binding EGF-like growth factor (HBEGF) in macrophages, which induces epithelial-to-mesenchymal transition (EMT) in cancer cells, thereby increasing metastasis. Macrophage stimulation by PM results in activation and subsequent nuclear translocation of the aryl hydrocarbon receptor and upregulation of HBEGF. Secreted HBEGF activates EGFR on the cancer cell surface to induce EMT, resulting in increased migration and invasion in vitro and increased metastasis in vivo. Therefore, our study reveals a critical PM-macrophage-cancer cell signaling axis mediating EMT and metastasis and provides an effective therapeutic approach for PM-induced malignancy.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Material Particulado
/
Transición Epitelial-Mesenquimal
/
Factor de Crecimiento Similar a EGF de Unión a Heparina
/
Macrófagos
/
Metástasis de la Neoplasia
Tipo de estudio:
Observational_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Exp Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2022
Tipo del documento:
Article