Células estaminais do cancro da mama hormonodependente apresentam características dos tumores de pior prognóstico triplos negativos

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Células estaminais do cancro da mama hormonodependente apresentam características dos tumores de pior prognóstico triplos negativos

Quarta, 10.01.2018

Na prática clínica, o cancro da mama é estratificado em três grupos: tumores que sobrexpressam HER-2, candidatos a terapêutica dirigida; tumores que expressam recetores hormonais, com indicação para terapêutica hormonal; e os tumores triplos negativos, para os quais não existem terapêuticas dirigidas. Assim, esta estratificação tem implicações terapêuticas e prognósticas.

As células estaminais do cancro constituem uma pequena população celular tumoral que se caracteriza pela sua importância na iniciação tumoral, progressão, metastização e resistência à terapêutica. Assim, o trabalho descrito no artigo “Mammospheres of hormonal recetor positive breast cancer diverge to triple-negative phenotype”, publicado na revista The Breast, compara as células estaminais do cancro considerando células tumorais da mama que expressam recetores hormonais e células tumorais da mama triplas negativas.

Foi possível isolar, através da realização sucessiva do ensaio de formação de esferas, células estaminais do cancro da mama provenientes tanto da população hormonodependente como da tripla negativa. De facto, a capacidade de obter células estaminais do cancro foi superior nas células triplas negativas, o que se pode correlacionar com o seu comportamento clínico mais agressivo. Foram identificados marcadores promissores, que se pretendem continuar a estudar, para avaliar a sua utilização como indicadores de progressão e também como eventuais alvos de atuação terapêutica. A perda de expressão de recetores hormonais e p53 evidenciaram que as células estaminais do cancro provenientes de tumores hormonodependentes apresentam um comportamento semelhante às células triplas negativas. Este dado é relevante na medida em que pode estar relacionado com casos de baixa resposta à hormonoterapia ou de recorrência.

 

Autores e Afiliações:

Laranjo M1, Carvalho MJ2, Costa T3, Alves A3, Oliveira RC4, Casalta-Lopes J5, Cordeiro P3, Botas F3, Abrantes AM6, Paiva A7, Oliveira C8, Botelho MF6

1 Biophysics Institute, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; CIMAGO, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; CNC.IBILI, University of Coimbra, Coimbra, Portugal. 

2 Biophysics Institute, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; CIMAGO, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Gynecology A Service, Coimbra Hospital and Universitary Centre, Coimbra, Portugal.

3 Biophysics Institute, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.

4 Biophysics Institute, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Pathology Service, Coimbra Hospital and Universitary Centre, Coimbra, Portugal.

5 Biophysics Institute, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; CIMAGO, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Radiation Oncology Department, Coimbra Hospital and Universitary Centre, Coimbra, Portugal.

6 Biophysics Institute, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; CIMAGO, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; CNC.IBILI, University of Coimbra, Coimbra, Portugal.

7 Cytometry Operational Management Unit, Clinical Pathology Service, Coimbra Hospital and Universitary Centre, Coimbra, Portugal.

8 CIMAGO, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.

 

Abstract:

Objectives: This study aimed to characterize mammospheres from hormonal receptor (HR) positive and triple-negative breast cancer (TNBC), hypothesizing a differential profile of CSC and differentiation markers, and a stemness enrichment when successive sphere forming-protocols are performed.

Methods: Breast cancer cells MCF-7 and HCC1806 were submitted to sphere-forming protocols. The first sphere generation (MS1) was cultured in adherent conditions (G1). This procedure was repeated and generations of mammospheres (MS1, MS2, and MS3) and sphere-derived cells in adherent conditions (G1, G2, and G3) were obtained. The mammosphere forming capacity, self-renewal, area and doubling time were evaluated. Flow cytometry regarding CD133, CD24, and CD44 and western-blot regarding aldehyde dehydrogenase (ALDH), hormonal receptors and P53 expression was performed. Results: Breast cancer cell lines harboured the capacity to form spheres, which originated derived adherent populations. The sphere-forming capacity was enhanced in HCC1806-MS3 compared to MS1. Self-renewal was higher in MCF-7 mammospheres, which also had an increased area. The putative CSC markers CD133 showed tendency to be enhanced in mammospheres but the CD44þ/CD24-/low phenotype was not identified. The expression of ALDH was greater in mammospheres from MCF-7 and HCC1806 than in the respectively derived adherent cells. The expression of oestrogen receptor (ER)-a, progesterone receptor (PR) and P53 decreased in MCF-7 spheres. ER-b expression was lower in mammospheres from both cell lines compared with parental and derived adherent populations. Conclusions: Loss of HR and P53 expression in HR-positive mammospheres evidences the minor population of CSC which shares characteristics with the TNBC phenotype.

 

Revista: The Breast

 

Link: http://www.thebreastonline.com/article/S0960-9776(17)30779-8/abstract