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Los factores producidos por el carcinoma activan las células mielóides a través de TLR2 para estimular la metástasis
Sunhwa Kim1, Hiroyuki Takahashi, Wan-Wan Lin
1Department of Pharmacology and Cancer Center, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA.
Nature
|January 6, 2009
Resumen
Las células cancerosas avanzadas, como el carcinoma de pulmón de Lewis (LLC), secretan versican. Esta molécula activa los macrófagos a través de los receptores tipo Toll (TLR), promoviendo la inflamación y mejorando la metástasis tumoral.
Área de la Ciencia:
- Oncología Oncología.
- Inmunología Inmunología.
- La bioquímica es la bioquímica.
Sus antecedentes:
- La progresión metastásica está influenciada por la genética de las células cancerosas y la inflamación del microambiente tumoral.
- Comprender el impacto de las células cancerosas en el microambiente inflamatorio es crucial.
Objetivo del estudio:
- Para identificar los factores de activación de los macrófagos secretados por los carcinomas metastásicos.
- Para aclarar el papel de estos factores en la promoción de la metástasis.
Principales métodos:
- Cribado bioquímico de los factores de activación de los macrófagos de las líneas celulares metastásicas de carcinoma de pulmón de Lewis (CLL).
- Identificación de versican a través de la purificación del medio acondicionado por LLC.
- Análisis de la participación del receptor Toll-like (TLR) en la activación y metástasis de los macrófagos.
Principales resultados:
- Las células del carcinoma de pulmón de Lewis (LLC) activaron potentemente los macrófagos, induciendo la interleucina-6 (IL-6) y el factor de necrosis tumoral alfa (TNF-alfa) a través de TLR2 y TLR6.
- Tanto el TNF-alfa como el TLR2 fueron esenciales para la metástasis de la LLC.
- El versicano proteoglicano de matriz extracelular fue identificado como un activador macrófago clave, actuando a través de los complejos TLR2:TLR6 y CD14.
- Versican mejoró el crecimiento metastásico de LLC al inducir la secreción de TNF-alfa de las células mieloides.
Conclusiones:
- Las células cancerosas avanzadas secuestran componentes del sistema inmunológico innato para fomentar un microambiente inflamatorio pro-metastásico.
- Versican secretado por las células cancerosas juega un papel importante en la promoción de la metástasis mediante la activación de las células mieloides y la conducción de la inflamación.
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