Generation of Breast Cancer Stem Cells through Epithelial-Mesenchymal Transition

Morel, Anne-Pierre; Lièvre, Marjory; Thomas, Clémence; Hinkal, George; Ansieau, Stéphane; Puisieux, Alain

doi:10.1371/journal.pone.0002888

Cited by 1,407 publications

(1,281 citation statements)

References 40 publications

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“…Reduced CD24 cell surface expression is associated with EMT, and has also been identified as a marker for tumorigenic self-renewing cancer stem cells. Human breast cancer cells with tumor-initiating potential have been identified as CD24 -/lo by their ability to initiate and form tumor in immune-compromised mice as well as the ability to grow as mammospheres in non-adhesive in vitro conditions [3,[9][10][11]. There is evidence that CD24 expression is dynamically regulated in tumor cell lines such that non-invasive CD24 + cells can give rise to invasive CD24 -/lo cells however, defining tumor-initiating cells (TICs) based on CD24 expression has been inconsistent between human xenograph and murine syngeneic animal models [2,10].…”

Section: Introductionmentioning

confidence: 99%

Separation and Characterization of Epithelial and Mesenchymal-like Murine Mammary Tumor Cells Reveals Epithelial Cell Differentiation Plasticity and Enhanced Tumorigenicity of Epithelial-enriched Tumor Cells

Palen

Jing²,

Weber³

et al. 2012

Cancer Microenvironment

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Tumors are composed of heterogeneous populations of cells including tumor-initiating cells (TICs) and metastatic precursors. While the origin of these cells is unknown, there is evidence that tumor cells can transdifferentiate from an epithelial to a mesenchymal phenotype, a property referred to as epithelial-to-mesenchymal transition (EMT). This cellular plasticity may explain the heterogeneous nature of tumors and differences in the tumorigenic and invasive properties of cells. Understanding the origin of these cells and the contribution of external factors that influence the acquisition of cellular properties is critical for the development of therapeutics to eradicate cancer. In this study, we show that primary murine tumor cells harvested from FVB/N Tg (MMTV/Neu) spontaneous mammary tumors possess differentiation plasticity and can be enriched to be epithelial or mesenchymal-like using selected culture media conditions, and we show evidence of EMT in a clonal population of primary epithelial tumor cells when cultured in fibroblast growth factor-1 (FGF-1) or transforming growth factor-β (TGF-β). We also determined that in contrast to the identification of mesenchymal-like tumor cells as TICs in orthotopic xenograph models of tumorigenicity, epithelial-enriched

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Section: Introductionmentioning

confidence: 99%

Separation and Characterization of Epithelial and Mesenchymal-like Murine Mammary Tumor Cells Reveals Epithelial Cell Differentiation Plasticity and Enhanced Tumorigenicity of Epithelial-enriched Tumor Cells

Palen

Jing²,

Weber³

et al. 2012

Cancer Microenvironment

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show abstract

“…On the other hand, immortalized mammary cell line such as HMLEs (Elenbaas et al, 2001) can be cultured in vitro for prolonged periods; however, they lack the ability to generate mammospheres (Mani et al, 2008;Morel et al, 2008), indicating the lack of stem-like properties. In this study, we have demonstrated the successful generation of a breast cell line, NBLE, which can be continuously propagated in vitro without losing stem-like properties.…”

Section: Discussionmentioning

confidence: 99%

Introduction of SV40ER and hTERT into mammospheres generates breast cancer cells with stem cell properties

et al. 2011

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“…8 In addition, the epithelial to mesenchymal transition program is closely linked to the acquisition of stem cell properties in other tumor cells, as defined by the acquisition of the CD44 high /CD24 low phenotype, in vitro self-renewal and in vivo tumor initiation capacities. 7,10 The epithelial to mesenchymal transition has also been implicated in the dissemination of primary tumors owing to invasion or intravasation, as well as to the generation of distant tumors by migrating cancer stem cells. 11 The Hippo pathway has been implicated in epithelial to mesenchymal transition and stemness, 12 and it is a pathway that coordinates cell proliferation, apoptosis, and differentiation associated with the regulation of organ development and regeneration.…”

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confidence: 99%

A role for the transducer of the Hippo pathway, TAZ, in the development of aggressive types of endometrial cancer

et al. 2015

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Although TAZ, the final effector of the Hippo pathway that modulates epithelial to mesenchymal transition and stemness, has been implicated in the development of different types of cancer, its role in endometrial cancer has not yet been studied. Thus, we evaluated the expression of TAZ in different types of endometrial cancer by immunohistochemistry. TAZ expression was detected in 76% of undifferentiated endometrial carcinomas, 54% of endometrial carcinosarcomas, 46% of endometrial serous carcinomas, 36% of grade 3 endometrioid carcinomas, and 18% of grade 1-2 endometrioid carcinomas, with statistically significant differences. We analyzed the WWTR1 gene that encodes TAZ by FISH and MassARRAY spectrometry, ruling out gene amplification and differential promoter methylation as the main mechanisms that modulate TAZ expression in endometrial tumors. However, we did detect a significant association between Scribble hypoexpression and delocalization with TAZ expression. Moreover, we demonstrated that TAZ promoted invasiveness, and it favored cell motility and tumor growth, in endometrial cancer cell lines. In addition, TAZ expression was associated with the transition from an epithelial to mesenchymal phenotype, both in vitro and in human tumors. Together, these data reveal a previously unknown role for TAZ and the Hippo pathway in the progression of aggressive subtypes of endometrial cancer. Modern Pathology (2015Pathology ( ) 28, 1492Pathology ( -1503 doi:10.1038/modpathol.2015 published online 18 September 2015 In developed countries, endometrial carcinoma is the most common malignant tumor of the female genital tract. 1 On the basis of epidemiological, clinical, pathological, and molecular features, endometrial carcinoma can be classified into at least two main categories: 2 type I estrogen-dependent carcinomas that account for 80-85% of cases and that are typically represented by low-grade (grade 1 and 2) endometrioid carcinomas, and type II endometrial carcinomas that are not estrogen dependent and that are mainly represented by a serous subtype but also by other high-grade histological tumors like clear cell or undifferentiated carcinomas. 2 In endometrial carcinoma, the epithelial to mesenchymal transition has been associated with high-grade and aggressive features. [3][4][5][6] Epithelial to

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Generation of Breast Cancer Stem Cells through Epithelial-Mesenchymal Transition

Cited by 1,407 publications

References 40 publications

Separation and Characterization of Epithelial and Mesenchymal-like Murine Mammary Tumor Cells Reveals Epithelial Cell Differentiation Plasticity and Enhanced Tumorigenicity of Epithelial-enriched Tumor Cells

Separation and Characterization of Epithelial and Mesenchymal-like Murine Mammary Tumor Cells Reveals Epithelial Cell Differentiation Plasticity and Enhanced Tumorigenicity of Epithelial-enriched Tumor Cells

Introduction of SV40ER and hTERT into mammospheres generates breast cancer cells with stem cell properties

A role for the transducer of the Hippo pathway, TAZ, in the development of aggressive types of endometrial cancer

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