Inflammation-induced hepatocellular carcinoma is dependent on CCR5 in mice.
Hepatology
; 58(3): 1021-30, 2013 Sep.
Article
em En
| MEDLINE
| ID: mdl-23526353
ABSTRACT
UNLABELLED Human hepatocellular carcinoma (HCC) is an inflammation-induced cancer, which is the third-leading cause of cancer mortality worldwide. We investigated the role of the chemokine receptors, CCR5 and CCR1, in regulating inflammation and tumorigenesis in an inflammation-induced HCC model in mice. Multidrug resistance 2 gene (Mdr2)-knockout (Mdr2-KO) mice spontaneously develop chronic cholestatic hepatitis and fibrosis that is eventually followed by HCC. We generated two new strains from the Mdr2-KO mouse, the Mdr2CCR5 and the Mdr2CCR1 double knockouts (DKOs), and set out to compare inflammation and tumorigenesis among these strains. We found that in Mdr2-KO mice lacking the chemokine receptor, CCR5 (Mdr2CCR5 DKO mice), but not CCR1 (Mdr2CCR1 DKO), macrophage recruitment and trafficking to the liver was significantly reduced. Furthermore, in the absence of CCR5, reduced inflammation was also associated with reduced periductal accumulation of CD24(+) oval cells and abrogation of fibrosis. DKO mice for Mdr2 and CCR5 exhibited a significant decrease in tumor incidence and size. CONCLUSIONS:
Our results indicate that CCR5 has a critical role in both the development and progression of liver cancer. Therefore, we propose that a CCR5 antagonist can serve for HCC cancer prevention and treatment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
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Receptores CCR5
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Hepatite Crônica
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Cirrose Hepática
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Neoplasias Hepáticas
Tipo de estudo:
Incidence_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Hepatology
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Israel