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Una ruta hematógena para las metástasis leptomeníngeas del medulloblastoma
Livia Garzia1, Noriyuki Kijima1, A Sorana Morrissy1
1Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
Cell
|February 24, 2018
Resumen
Las células cancerosas del meduloblastoma pueden viajar a través del torrente sanguíneo para propagarse, formando metástasis leptomeníngeas. Dirigirse a la quimioquina CCL2 puede ofrecer nuevas formas de diagnosticar y tratar la diseminación del meduloblastoma.
Área de la Ciencia:
- En el campo de la oncología
- La neurociencia
- Investigación de las Metástasis del Cáncer
Sus antecedentes:
- La mortalidad por meduloblastoma se debe principalmente a la enfermedad metastásica, sin embargo, la investigación está limitada por la falta de muestras metastásicas.
- Las metástasis del meduloblastoma se producen predominantemente en las superficies leptomeníngeas, lo que sugiere la diseminación del líquido cefalorraquídeo.
- La comprensión actual de la propagación del meduloblastoma es incompleta, lo que dificulta las estrategias de tratamiento efectivas.
Objetivo del estudio:
- Investigar la presencia y el papel de las células tumorales circulantes (CTC) en el meduloblastoma.
- Determinar si las CTC del meduloblastoma pueden diseminarse a través del torrente sanguíneo para formar metástasis leptomeníngeas.
- Identificar los mecanismos moleculares que impulsan la diseminación leptomeníngea, específicamente el papel de la CCL2.
Principales métodos:
- Detección de células tumorales circulantes de meduloblastoma (CTC) en pacientes no tratados.
- Estudios in vivo utilizando xenografts de flanco y parabiosis para modelar la propagación hematógena.
- Análisis de la expresión de la quimioquina CCL2 en las metástasis leptomeníngeas del medulloblastoma.
Principales resultados:
- Pruebas de CTC de meduloblastoma en pacientes no tratados.
- Demostración de que las CTC del meduloblastoma se propagan por la sangre para formar metástasis leptomeníngeas in vivo.
- Alta expresión de CCL2 en las metástasis leptomeníngeas, con CCL2 suficiente para impulsar la diseminación.
Conclusiones:
- El meduloblastoma puede diseminarse hematógenamente a través de las células tumorales circulantes.
- La metástasis leptomeníngea está impulsada por la expresión de CCL2.
- La diseminación hematógena proporciona nuevos objetivos diagnósticos y terapéuticos para el meduloblastoma.
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