Human Primary Breast Cancer Stem Cells Are Characterized by Epithelial-Mesenchymal Plasticity.

Juliane Strietz,Stella S Stepputtis,Peter Bronsert,Jochen Maurer,Elmar Stickeler,Marie Follo

doi:10.3390/ijms22041808

Abstract

Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, with only limited treatment options available. Recently, cancer stem cells (CSCs) have emerged as the potential drivers of tumor progression due to their ability to both self-renew and give rise to differentiated progeny. The CSC state has been linked to the process of epithelial-mesenchymal transition (EMT) and to the highly flexible state of epithelial-mesenchymal plasticity (EMP). We aimed to establish primary breast cancer stem cell (BCSC) cultures isolated from TNBC specimens. These cells grow as tumor spheres under anchorage-independent culture conditions in vitro and reliably form tumors in mice when transplanted in limiting dilutions in vivo. The BCSC xenograft tumors phenocopy the original patient tumor in architecture and gene expression. Analysis of an EMT-related marker profile revealed the concomitant expression of epithelial and mesenchymal markers suggesting an EMP state for BCSCs of TNBC. Furthermore, BCSCs were susceptible to stimulation with the EMT inducer TGF-β1, resulting in upregulation of mesenchymal genes and enhanced migratory abilities. Overall, primary BCSC cultures are a promising model close to the patient that can be used both in vitro and in vivo to address questions of BCSC biology and evaluate new treatment options for TNBC.

Highlights

IntroductionBreast cancer is the most frequently diagnosed cancer in women, and one of the leading causes of cancer death [1]
Introduction published maps and institutional affilBreast cancer is the most frequently diagnosed cancer in women, and one of the leading causes of cancer death [1]
Over the last few years, we established a panel of primary breast cancer stem cell lines that we isolated from triplenegative breast cancer (TNBC) patient tumor tissues

Summary

Introduction

Breast cancer is the most frequently diagnosed cancer in women, and one of the leading causes of cancer death [1]. It is very heterogeneous in its histology, therapeutic response, metastatic behavior, and patient outcome. Among the various intrinsic subtypes [2], triplenegative breast cancer (TNBC) is the most aggressive one. 10–17% of all breast cancer cases [3]. TNBC is characterized by the lack of estrogen receptor (ER) and progesterone receptor (PR) expression, as well as by the absence of human epidermal growth factor receptor 2 (HER2) overexpression. Presenting no molecular weak points, tumors of this subtype are generally difficult to treat and have a poor prognosis [4,5]

Objectives

Methods

Results

Discussion

Conclusion