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Eur Biophys J. 2019 Oct;48(7):673-684. doi: 10.1007/s00249-019-01393-0. Epub 2019 Sep 4.

Phenotypic, structural, and ultrastructural analysis of triple-negative breast cancer cell lines and breast cancer stem cell subpopulation.

Author information

1
Serviço de Biologia Celular, Diretoria de Pesquisa e Desenvolvimento, Fundação Ezequiel Dias, Rua Conde Pereira Carneiro 80, Gameleira, Belo Horizonte, Minas Gerais, 30510-010, Brazil.
2
Laboratório de Patologia Comparada, Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos 6627, Pampulha, Belo Horizonte, Minas Gerais, 31270-901, Brazil.
3
Laboratório de Imunopatologia Keizo Asami (LIKA), Universidade Federal de Pernambuco (UFPE), Avenida Professor Moraes Rego, s/n, Campus da UFPE, Cidade Universitária, Recife, Pernambuco, 50740-465, Brazil.
4
Instituto Aggeu Magalhães (IAM), Fundação Oswaldo Cruz (FIOCRUZ), Avenida Professor Moraes Rego, s/n, Campus da UFPE, Cidade Universitária, Recife, Pernambuco, 50670-420, Brazil.
5
Serviço de Biologia Celular, Diretoria de Pesquisa e Desenvolvimento, Fundação Ezequiel Dias, Rua Conde Pereira Carneiro 80, Gameleira, Belo Horizonte, Minas Gerais, 30510-010, Brazil. luciana.silva@funed.mg.gov.br.

Abstract

Triple negative breast cancer (TNBC) is a highly heterogeneous disease, which influences the therapeutic response and makes difficult the discovery of effective targets. This heterogeneity is attributed to the presence of breast cancer stem cells (BCSCs), which determines resistance to chemotherapy and subsequently disease recurrence and metastasis. In this context, this work aimed to evaluate the morphological and phenotypic cellular heterogeneity of two TNBC cell lines cultured in monolayer and tumorsphere (TS) models by fluorescence and electron microscopy and flow cytometry. The BT-549 and Hs 578T analyses demonstrated large phenotypic and morphological heterogeneity between these cell lines, as well as between the cell subpopulations that compose them. BT-549 and Hs 578T are heterogeneous considering the cell surface marker CD44 and CD24 expression, characterizing BCSC mesenchymal-like cells (CD44+/CD24-), epithelial cells (CD44-/CD24+), hybrid cells with mesenchymal and epithelial features (CD44+/CD24+), and CD44-/CD24- cells. BCSC epithelial-like cells (ALDH+) were found in BT-549, BT-549 TS, and Hs 578T TS; however, only BT-549 TS showed a high ALDH activity. Ultrastructural characterization showed the heterogeneity within and among BT-549 and Hs 578T in monolayer and TS models being formed by more than one cellular type. Further, the mesenchymal characteristic of these cells is demonstrated by E-cadherin absence and filopodia. It is well known that tumor cell heterogeneity can influence survival, therapy responses, and the rate of tumor growth. Thus, molecular understanding of this heterogeneity is essential for the identification of potential therapeutic options and vulnerabilities of oncological patients.

KEYWORDS:

Cancer stem cell; Cell line; Cellular heterogeneity; Triple negative breast cancer

PMID:
31485678
DOI:
10.1007/s00249-019-01393-0

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