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

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

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Monday, 23.11.2020

Authors and Affiliations:

Maria Rita Dionísio 1,2,3, André F Vieira 1,2, Rita Carvalho 1,2, Inês Conde 1,2, Mónica Oliveira 1,2, Madalena Gomes 1,2, Marta T Pinto 1,2,4, Pedro Pereira 3, José Pimentel 3, Cristiano Souza 5, Márcia M C Marques 6,7, Vinícius Duval da Silva 8, Alison Barroso 5, Daniel Preto 5, Jorge F Cameselle-Teijeiro 9, Fernando Schmitt 1,2,10, Ana Sofia Ribeiro 1,2, Joana Paredes 1,2,10

1Epithelial Interactions in Cancer (EPIC) group, i3S, Institute of Investigation and Innovation in Health, University of Porto, 4200-135 Porto, Portugal.

2IPATIMUP- Institute of Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal.

3Centro Hospitalar de Lisboa Norte, 1649-035 Lisboa, Portugal.

4In vivo CAM assays, i3S - Institute of Investigation and Innovation in Health, University of Porto, 4200-135 Porto, Portugal.

5Department of Breast and Gynecologic Oncology, Barretos Cancer Hospital, Barretos-SP 14784-400, Brazil.

6Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos-SP 14784-400, Brazil.

7Barretos School of Health Sciences - FACISB, Barretos-SP 14784-400, Brazil.

8Department of Pathology, Barretos Cancer Hospital, Barretos-SP 14784-400, Brazil.

9Department of Pathology, Complejo Hospitalario Universitário de Vigo (CHUVI) 36204 Vigo, Spain.

10Department of Pathology, Faculty of Medicine of Porto University (FMUP), 4200-135 Porto, Portugal.

 

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.

 

Journal: Cells

 

Link: https://www.mdpi.com/2073-4409/9/11/2442

 

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