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Nature ; 543(7647): 676-680, 2017 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-28358093

RESUMEN

Cancer stem cells (CSCs) have been hypothesized to represent the driving force behind tumour progression and metastasis, making them attractive cancer targets. However, conclusive experimental evidence for their functional relevance is still lacking for most malignancies. Here we show that the leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) identifies intestinal CSCs in mouse tumours engineered to recapitulate the clinical progression of human colorectal cancer. We demonstrate that selective Lgr5+ cell ablation restricts primary tumour growth, but does not result in tumour regression. Instead, tumours are maintained by proliferative Lgr5- cells that continuously attempt to replenish the Lgr5+ CSC pool, leading to rapid re-initiation of tumour growth upon treatment cessation. Notably, CSCs are critical for the formation and maintenance of liver metastasis derived from colorectal cancers. Together, our data highlight distinct CSC dependencies for primary versus metastasic tumour growth, and suggest that targeting CSCs may represent a therapeutic opportunity for managing metastatic disease.


Asunto(s)
Neoplasias Colorrectales/patología , Metástasis de la Neoplasia/patología , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Receptores Acoplados a Proteínas G/metabolismo , Animales , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Proliferación Celular , Separación Celular , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Inyecciones Subcutáneas , Intestinos/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Ratones , Metástasis de la Neoplasia/tratamiento farmacológico , Células Madre Neoplásicas/efectos de los fármacos , Organoides/patología , Organoides/trasplante , Receptores Acoplados a Proteínas G/análisis
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