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Los osteoblastos suministran remotamente a los tumores pulmonares los neutrófilos que promueven el cáncer
Camilla Engblom1,2, Christina Pfirschke1, Rapolas Zilionis3,4
1Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA 02114, USA.
Science (New York, N.Y.)
|December 2, 2017
Resumen
Los adenocarcinomas pulmonares activan remotamente los osteoblastos óseos, que suministran los neutrófilos que promueven el tumor. La reducción de las células que expresan osteocalcina suprime la respuesta de los neutrófilos y el crecimiento del tumor pulmonar.
Área de la Ciencia:
- En el campo de la oncología
- Inmunología
- Biología ósea
Sus antecedentes:
- Las células mieloides en los tumores pueden promover el crecimiento del cáncer.
- El papel del entorno del huésped sistémico en el crecimiento del tumor no se entiende bien.
- Las interacciones inmunotumorales locales han sido ampliamente estudiadas.
Objetivo del estudio:
- Investigar la contribución del entorno del huésped sistémico al crecimiento del adenocarcinoma pulmonar.
- Identificar los mecanismos por los que el cáncer de pulmón no metastásico influye en el microambiente óseo.
- Explorar el papel de los osteoblastos y los subconjuntos específicos de neutrófilos en la progresión del cáncer.
Principales métodos:
- Se estudió el adenocarcinoma pulmonar en ratones y 70 pacientes con cáncer.
- Investigar cambios inducidos por el cáncer en la actividad del estroma óseo.
- Se analizó el papel de las células osteoblásticas que expresan osteocalcina (Ocn +).
- Se examinó el impacto de las células Ocn+ en los neutrófilos SiglecFhigh que se infiltran en el tumor.
- Se evaluó el efecto de la reducción del número de células Ocn+ en el crecimiento tumoral.
Principales resultados:
- Los adenocarcinomas pulmonares aumentan la actividad del estroma óseo, incluso sin metástasis ósea.
- Las células osteoblásticas que expresan osteocalcina están involucradas en este fenotipo óseo inducido por el cáncer.
- Las células Ocn+ suministran de forma remota los neutrófilos SiglecF que promueven el cáncer.
- La reducción del número de células Ocn+ suprimió la respuesta de los neutrófilos y el crecimiento del tumor pulmonar.
Conclusiones:
- Los osteoblastos actúan como reguladores remotos de la progresión del cáncer de pulmón.
- Los neutrófilos altos de SiglecF son efectores clave de las células mieloides en la respuesta protumoral impulsada por los osteoblastos.
- La orientación de las interacciones entre los osteoblastos y los neutrófilos puede ofrecer nuevas estrategias terapéuticas para el cáncer de pulmón.
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