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Las neuronas nociceptivas promueven la progresión del tumor gástrico a través de un eje CGRP-RAMP1
Xiaofei Zhi1,2, Feijing Wu1, Jin Qian1
1Division of Digestive and Liver Diseases, Irving Cancer Research Center, Columbia University Medical Center, New York, NY, USA.
Nature
|February 19, 2025
Resumen
El cáncer gástrico explota los nervios sensoriales periféricos para crecer y propagarse. Dirigirse a estas conexiones nerviosas del cáncer, específicamente utilizando inhibidores de CGRP, ofrece una nueva estrategia terapéutica prometedora.
Área de la Ciencia:
- La neurociencia
- En el campo de la oncología
- Biología del cáncer
Sus antecedentes:
- Las células cancerosas pueden aprovechar las neuronas para sobrevivir y crecer.
- Los circuitos neuronales están implicados en los cánceres del sistema nervioso central.
- La participación del sistema nervioso periférico en el cáncer gástrico sigue siendo menos comprendida.
Objetivo del estudio:
- Para investigar la interacción entre los nervios periféricos y el cáncer gástrico.
- Para identificar los tipos específicos de neuronas sensoriales involucradas.
- Para explorar el potencial terapéutico de dirigirse a la comunicación entre el cáncer y el nervio.
Principales métodos:
- Usó modelos de ratón de cáncer gástrico.
- Empleó técnicas de rastreo neuronal.
- Sistemas de co-cultura 3D establecidos.
- Quimogenética aplicada y optogenética para la manipulación neuronal.
- Intervenciones farmacológicas investigadas dirigidas a las neuronas sensoriales y al CGRP.
Principales resultados:
- Los nervios nociceptivos, principalmente las neuronas peptidérgicas CGRP +, extensivamente inervaron los tumores gástricos de una manera dependiente del NGF.
- Las neuronas sensoriales conectadas directamente con los esferoides del cáncer gástrico.
- La activación de las neuronas sensoriales promovió el crecimiento tumoral y la metástasis a través de la señalización de calcio en las células cancerosas.
- La inhibición de las neuronas sensoriales o CGRP suprimió la progresión tumoral y mejoró la supervivencia.
- Demostró un circuito neuronal funcional de las células cancerosas.
Conclusiones:
- Estableció un nuevo circuito de neuronas sensoriales periféricas de células cancerosas en el cáncer gástrico.
- Destacó el papel de las neuronas peptidérgicas CGRP+ en la promoción del crecimiento y la metástasis del tumor gástrico.
- Identificó la vía nerviosa del cáncer como un objetivo terapéutico potencial para el tratamiento del cáncer gástrico.
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