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La proximidad sináptica permite que la señalización NMDAR promueva la metástasis cerebral
Qiqun Zeng1,2, Iacovos P Michael1,2, Peng Zhang3
1Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland.
Nature
|September 20, 2019
Resumen
Las células de cáncer de mama con metástasis en el cerebro secuestran las vías neuronales. Forman pseudo-sinapsis con las neuronas para activar los receptores de N-metil-D-aspartato (NMDAR), impulsando la metástasis cerebral.
Área de la Ciencia:
- En el campo de la oncología
- La neurociencia
- Biología celular
Sus antecedentes:
- La metástasis, la propagación del cáncer a órganos distantes, es la principal causa de muertes relacionadas con el cáncer.
- La metástasis de mama al cerebro (B2BM) es una complicación frecuente y devastadora del cáncer de mama, particularmente en los subtipos agresivos.
- Los mecanismos específicos que impulsan la preferencia del cáncer de mama por las metástasis cerebrales han permanecido en gran medida poco claros.
Objetivo del estudio:
- Para aclarar los mecanismos moleculares subyacentes a la colonización preferencial del cerebro por el cáncer de mama.
- Para investigar el papel de las vías de señalización neuronal en la metástasis de mama al cerebro.
- Identificar posibles objetivos terapéuticos para la prevención o el tratamiento de las metástasis cerebrales.
Principales métodos:
- Análisis de células de cáncer de mama humano y de ratón y de tejido cerebral.
- Investigación de las vías de señalización del receptor de N-metil-D-aspartato (NMDAR).
- Sistemas de co-cultivo para modelar las interacciones entre células cancerosas y neuronas y la formación de sinapsis.
Principales resultados:
- Las células de metástasis de mama al cerebro activan los receptores de N-metil-D-aspartato (NMDAR), una vía de señalización neuronal crucial para la colonización del cerebro.
- Las células B2BM expresan NMDAR pero segregan una cantidad insuficiente de glutamato para la señalización autocrina.
- Las células cancerosas forman sinapsis pseudo-tripartitas con neuronas glutamatérgicas, lo que permite la activación de NMDAR y la conducción de la metástasis cerebral.
- La activación de NMDAR en B2BM está asociada con un mal pronóstico.
Conclusiones:
- Las células de cáncer de mama explotan la señalización neuronal de glutamato a través de NMDAR para hacer metástasis en el cerebro.
- La formación de pseudo-sinapsis entre las células cancerosas y las neuronas es un mecanismo clave para la metástasis cerebral.
- Dirigirse a la vía NMDAR o a estas pseudo-sinapsis puede ofrecer nuevas estrategias terapéuticas contra la B2BM.
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