Membrane Cholesterol Efflux Drives Tumor-Associated Macrophage Reprogramming and Tumor Progression.
Cell Metab
; 29(6): 1376-1389.e4, 2019 06 04.
Article
en En
| MEDLINE
| ID: mdl-30930171
ABSTRACT
Macrophages possess intrinsic tumoricidal activity, yet tumor-associated macrophages (TAMs) rapidly adopt an alternative phenotype within the tumor microenvironment that is marked by tumor-promoting immunosuppressive and trophic functions. The mechanisms that promote such TAM polarization remain poorly understood, but once identified, they may represent important therapeutic targets to block the tumor-promoting functions of TAMs and restore their anti-tumor potential. Here, we have characterized TAMs in a mouse model of metastatic ovarian cancer. We show that ovarian cancer cells promote membrane-cholesterol efflux and depletion of lipid rafts from macrophages. Increased cholesterol efflux promoted IL-4-mediated reprogramming, including inhibition of IFNγ-induced gene expression. Genetic deletion of ABC transporters, which mediate cholesterol efflux, reverts the tumor-promoting functions of TAMs and reduces tumor progression. These studies reveal an unexpected role for membrane-cholesterol efflux in driving TAM-mediated tumor progression while pointing to a potentially novel anti-tumor therapeutic strategy.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Membrana Celular
/
Colesterol
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Reprogramación Celular
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Microambiente Tumoral
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Macrófagos
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Neoplasias
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Año:
2019
Tipo del documento:
Article