BR-BCSC Signature: The Cancer Stem Cell Profile Enriched in Brain Metastases that Predicts a Worse Prognosis in Lymph Node-Positive Breast Cancer
Identificadores
Identificadores
URI: http://hdl.handle.net/20.500.11940/16749
PMID: 33182375
DOI: 10.3390/cells9112442
ISSN: 2073-440
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Fecha de publicación
2020Título de revista
Cells
Tipo de contenido
Journal Article
DeCS
pronóstico | animales | análisis multifactorial | neoplasias cerebrales | células madre neoplásicas | ganglios linfáticos | neoplasias de la mama | carcinogénesis | embrión de pollo | membrana corioalantoides | estimación de Kaplan-Meier | línea celular | humanos | modelos de riesgos proporcionales | ratonesMeSH
Proportional Hazards Models | Brain Neoplasms | Multivariate Analysis | Breast Neoplasms | Chick Embryo | Mice | Lymph Nodes | Animals | Chorioallantoic Membrane | Cell Line | Humans | Carcinogenesis | Neoplastic Stem Cells | Kaplan-Meier Estimate | PrognosisResumen
Brain metastases remain an unmet clinical need in breast oncology, being frequently found in HER2-overexpressing and triple-negative carcinomas. These tumors were reported to be highly cancer stem-like cell-enriched, suggesting that brain metastases probably arise by the seeding of cancer cells with stem features. Accordingly, we found that brain-tropic breast cancer cells show increased stem cell activity and tumorigenic capacity in the chick embryo choriallantoic membrane when compared to the parental cell line. These observations were supported by a significant increase in their stem cell frequency and by the enrichment for the breast cancer stem cell (BCSC) phenotype CD44(+)CD24(-/low). Based on this data, the expression of BCSC markers (CD44, CD49f, P-cadherin, EpCAM, and ALDH1) was determined and found to be significantly enriched in breast cancer brain metastases when compared to primary tumors. Therefore, a brain (BR)-BCSC signature was defined (3-5 BCSC markers), which showed to be associated with decreased brain metastases-free and overall survival. Interestingly, this signature significantly predicted a worse prognosis in lymph node-positive patients, acting as an independent prognostic factor. Thus, an enrichment of a BCSC signature was found in brain metastases, which can be used as a new prognostic factor in clinically challenging breast cancer patients.