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

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2020 Nov 13

PMID 33182375

Citations 10

Authors

Maria Rita Dionisio

Andre F Vieira

Rita Carvalho

Ines Conde

Monica Oliveira

Madalena Gomes

Marta T Pinto

Pedro Pereira

Jose Pimentel

Cristiano Souza

Marcia M C Marques

Vinicius Duval da Silva

Alison Barroso

Daniel Preto

Jorge F Cameselle-Teijeiro

Fernando Schmitt

Ana Sofia Ribeiro

Joana Paredes

Affiliations

Soon will be listed here.

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 CD44CD24. 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.

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