Environmental and genetic activation of a brain-adipocyte BDNF/leptin axis causes cancer remission and inhibition.
Cell
; 142(1): 52-64, 2010 Jul 09.
Article
em En
| MEDLINE
| ID: mdl-20603014
ABSTRACT
Cancer is influenced by its microenvironment, yet broader, environmental effects also play a role but remain poorly defined. We report here that mice living in an enriched housing environment show reduced tumor growth and increased remission. We found this effect in melanoma and colon cancer models, and that it was not caused by physical activity alone. Serum from animals held in an enriched environment (EE) inhibited cancer proliferation in vitro and was markedly lower in leptin. Hypothalamic brain-derived neurotrophic factor (BDNF) was selectively upregulated by EE, and its genetic overexpression reduced tumor burden, whereas BDNF knockdown blocked the effect of EE. Mechanistically, we show that hypothalamic BDNF downregulated leptin production in adipocytes via sympathoneural beta-adrenergic signaling. These results suggest that genetic or environmental activation of this BDNF/leptin axis may have therapeutic significance for cancer.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Meio Social
/
Transdução de Sinais
/
Neoplasias do Colo
/
Fator Neurotrófico Derivado do Encéfalo
/
Leptina
/
Hipotálamo
/
Melanoma
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cell
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos