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Un ligando endógeno promotor de tumores del receptor de hidrocarburos de arilo humano
Christiane A Opitz1, Ulrike M Litzenburger, Felix Sahm
1Department of Neurooncology, Neurology Clinic and National Center for Tumor Diseases, University Hospital of Heidelberg, 69120 Heidelberg, Germany.
Nature
|October 7, 2011
Resumen
Los investigadores identificaron la kynurenina (Kyn), un metabolito del triptófano (Trp), como un ligando endógeno para el receptor de hidrocarburos de arilo (AHR). Esta vía TDO-AHR promueve el crecimiento tumoral y la supresión inmune, lo que afecta la progresión del cáncer.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología del cáncer Biología del cáncer.
- Biología Molecular Biología Molecular
Sus antecedentes:
- El receptor de hidrocarburos de arilo (AHR, por sus siglas en inglés) es activado por toxinas ambientales e involucrado en procesos celulares.
- El ligando endógeno para AHR bajo condiciones fisiológicas sigue sin ser identificado.
Objetivo del estudio:
- Para identificar un ligando endógeno para el AHR humano.
- Investigar el papel de la vía TDO-AHR en la biología del cáncer y las respuestas inmunológicas.
Principales métodos:
- Identificación de la kynurenina (Kyn) como un ligando endógeno de la AHR.
- Análisis de la actividad de la triptófano-2,3-dioxigenasa (TDO) en las células tumorales.
- Evaluación del papel de la vía TDO-AHR en la supresión inmune tumoral, la supervivencia y la motilidad.
- Correlación de la actividad de la vía TDO-AHR con la progresión del tumor cerebral humano y la supervivencia.
Principales resultados:
- La kynurenina (Kyn), un catabólito del triptófano (Trp), se identifica como un nuevo ligando endógeno para el AHR humano.
- Las células tumorales humanas generan Kyn de manera constitutiva a través de la triptófano-2,3-dioxigenasa (TDO).
- El Kyn derivado de TDO suprime las respuestas inmunes antitumorales y promueve la supervivencia y la motilidad de las células tumorales a través de AHR.
- La vía TDO-AHR está activa en los tumores cerebrales humanos, correlacionándose con la progresión maligna y la pobre supervivencia.
Conclusiones:
- Kynurenine (Kyn) es un ligando endógeno no reconocido previamente que activa el AHR.
- La vía TDO-AHR representa un nuevo mecanismo para la supresión inmune y la progresión tumoral.
- Esta vía tiene implicaciones significativas para el cáncer y la biología inmune, ofreciendo objetivos terapéuticos potenciales.
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