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Article

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

1
Epithelial Interactions in Cancer (EPIC) group, i3S, Institute of Investigation and Innovation in Health, University of Porto, 4200-135 Porto, Portugal
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IPATIMUP- Institute of Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal
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Centro Hospitalar de Lisboa Norte, 1649-035 Lisboa, Portugal
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In vivo CAM assays, i3S - Institute of Investigation and Innovation in Health, University of Porto, 4200-135 Porto, Portugal
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Department of Breast and Gynecologic Oncology, Barretos Cancer Hospital, Barretos-SP 14784-400, Brazil
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Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos-SP 14784-400, Brazil
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Barretos School of Health Sciences - FACISB, Barretos-SP 14784-400, Brazil
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Department of Pathology, Barretos Cancer Hospital, Barretos-SP 14784-400, Brazil
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Department of Pathology, Complejo Hospitalario Universitário de Vigo (CHUVI) 36204 Vigo, Spain
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Department of Pathology, Faculty of Medicine of Porto University (FMUP), 4200-135 Porto, Portugal
*
Author to whom correspondence should be addressed.
Cells 2020, 9(11), 2442; https://doi.org/10.3390/cells9112442
Received: 18 September 2020 / Revised: 30 October 2020 / Accepted: 4 November 2020 / Published: 9 November 2020
(This article belongs to the Special Issue Cancer Stem Cells (CSC))
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. View Full-Text
Keywords: breast cancer; cancer stem cells; stem cell biology; prognostic factors breast cancer; cancer stem cells; stem cell biology; prognostic factors
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MDPI and ACS Style

Dionísio, M.R.; Vieira, A.F.; Carvalho, R.; Conde, I.; Oliveira, M.; Gomes, M.; Pinto, M.T.; Pereira, P.; Pimentel, J.; Souza, C.; Marques, M.M.C.; Duval da Silva, V.; Barroso, A.; Preto, D.; Cameselle-Teijeiro, J.F.; Schmitt, F.; Ribeiro, A.S.; Paredes, J. BR-BCSC Signature: The Cancer Stem Cell Profile Enriched in Brain Metastases that Predicts a Worse Prognosis in Lymph Node-Positive Breast Cancer. Cells 2020, 9, 2442. https://doi.org/10.3390/cells9112442

AMA Style

Dionísio MR, Vieira AF, Carvalho R, Conde I, Oliveira M, Gomes M, Pinto MT, Pereira P, Pimentel J, Souza C, Marques MMC, Duval da Silva V, Barroso A, Preto D, Cameselle-Teijeiro JF, Schmitt F, Ribeiro AS, Paredes J. BR-BCSC Signature: The Cancer Stem Cell Profile Enriched in Brain Metastases that Predicts a Worse Prognosis in Lymph Node-Positive Breast Cancer. Cells. 2020; 9(11):2442. https://doi.org/10.3390/cells9112442

Chicago/Turabian Style

Dionísio, Maria R., 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 S. Ribeiro, and Joana Paredes. 2020. "BR-BCSC Signature: The Cancer Stem Cell Profile Enriched in Brain Metastases that Predicts a Worse Prognosis in Lymph Node-Positive Breast Cancer" Cells 9, no. 11: 2442. https://doi.org/10.3390/cells9112442

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