BR-BCSC Signature: The Cancer Stem Cell Profile Enriched in Brain Metastases that Predicts a Worse Prognosis in Lymph Node-Positive Breast Cancer.

Abstract

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.

• Authors: Maria Rita Dionísio, André F Vieira, Rita Carvalho, Inês Conde, Mónica Oliveira, Madalena Gomes, Marta T Pinto, Pedro Pereira, José Pimentel, Cristiano Souza, Márcia M C Marques, Vinícius Duval da Silva, Alison Barroso, Daniel Preto, Jorge F Cameselle-Teijeiro, Fernando Schmitt, Ana Sofia Ribeiro, Joana Paredes
• Journal: Cells (Cells) Vol. 9 Issue 11 (11 09 2020) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 33182375 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor

Topics

• Animals
• Biomarkers, Tumor (metabolism)
• Brain Neoplasms (pathology)
• Breast Neoplasms (pathology)
• Carcinogenesis (pathology)
• Cell Line, Tumor
• Chick Embryo
• Chorioallantoic Membrane (pathology)
• Female
• Humans
• Kaplan-Meier Estimate
• Lymph Nodes (pathology)
• Mice
• Multivariate Analysis
• Neoplastic Stem Cells (pathology)
• Prognosis
• Proportional Hazards Models