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La respuesta del tumor a la radioterapia regulada por la apoptosis de las células endoteliales
Monica Garcia-Barros1, Francois Paris, Carlos Cordon-Cardo
1Laboratory of Signal Transduction, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Science (New York, N.Y.)
|May 17, 2003
Resumen
La respuesta del tumor a la radioterapia depende tanto del tipo de célula cancerosa como de la sensibilidad de los vasos sanguíneos. El deterioro de la apoptosis endotelial en la vasculatura tumoral conduce a la resistencia a la radiación, destacando el daño microvascular como un factor clave en los resultados del tratamiento del cáncer.
Área de la Ciencia:
- Oncología Oncología.
- Biología del cáncer Biología del cáncer.
- Radioncología Oncología de Radiación.
Sus antecedentes:
- La radioterapia es un tratamiento común para el cáncer, que afecta a aproximadamente el 50% de los pacientes.
- La respuesta del tumor a la radiación está influenciada por las características de las células tumorales y el microambiente tumoral.
- El papel de la sensibilidad microvascular en la respuesta a la radiación requiere más investigación.
Objetivo del estudio:
- Para investigar la hipótesis de que la respuesta del tumor a la radioterapia está determinada por la sensibilidad microvascular.
- Para explorar el impacto de la apoptosis endotelial en el crecimiento tumoral y la resistencia a la radiación.
- Para determinar si el daño microvascular influye en la respuesta de las células tumorales a dosis de radiación clínicamente relevantes.
Principales métodos:
- Utilizado MCA/129 fibrosarcomas y melanomas B16F1 en ratones genéticamente modificados.
- Comparación del crecimiento tumoral y la apoptosis endotelial microvascular en ratones resistentes a la apoptosis (con deficiencia de esfingomielinasa ácida o con deficiencia de Bax) frente a ratones de tipo salvaje.
- Evaluación de la respuesta tumoral a una sola dosis de radiación de hasta 20 grays (Gy).
Principales resultados:
- Los tumores crecidos en ratones resistentes a la apoptosis mostraron una reducción significativa de la apoptosis endotelial microvascular basal.
- Estos tumores exhibieron un crecimiento 200-400% más rápido en comparación con los tumores en ratones de tipo salvaje.
- Los tumores en ratones resistentes a la apoptosis demostraron una reducción de la apoptosis endotelial tras la irradiación y fueron resistentes a dosis de radiación de hasta 20 Gy.
- Los tumores en ratones de tipo salvaje mostraron sensibilidad a la radiación.
Conclusiones:
- La apoptosis endotelial actúa como un factor homeostático que regula el crecimiento tumoral dependiente de la angiogénesis.
- La sensibilidad microvascular, específicamente la apoptosis endotelial, es un determinante crítico de la respuesta del tumor a la radioterapia.
- Dirigirse al daño microvascular podría ser una estrategia para mejorar la eficacia de la radioterapia en el tratamiento del cáncer.
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