Generation of Breast Cancer Stem Cells through Epithelial-Mesenchymal Transition

University of Helsinki, Finland
PLoS ONE (Impact Factor: 3.53). 02/2008; 3(8):e2888. DOI: 10.1371/journal.pone.0002888
Source: PubMed

ABSTRACT Recently, two novel concepts have emerged in cancer biology: the role of so-called "cancer stem cells" in tumor initiation, and the involvement of an epithelial-mesenchymal transition (EMT) in the metastatic dissemination of epithelial cancer cells. Using a mammary tumor progression model, we show that cells possessing both stem and tumorigenic characteristics of "cancer stem cells" can be derived from human mammary epithelial cells following the activation of the Ras-MAPK pathway. The acquisition of these stem and tumorigenic characters is driven by EMT induction.

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Available from: Clémence Thomas, Aug 10, 2015
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    • "Following the discovery that EMT generates CSCs (Mani et al., 2008; Morel et al., 2008), efforts have focused on targeting mesenchymal cells within breast cancer cell populations (Gupta et al., 2009; Tam et al., 2013). However, our data indicate that transient Twist1 activation enabled long-term invasive growth by promoting coexistence of epithelial and mesenchymal traits, whereas constitutive Twist1 activation switched cells to a migratory, nonproliferative state. "
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    ABSTRACT: During epithelial-mesenchymal transition (EMT), apical-basal polarized epithelial cells are converted to front-to-back polarized mesenchymal cells with unrestricted motility (Lamouille et al., 2014). EMT programs effect morphogenetic steps during embryogenesis and are orchestrated by pleiotropic transcription factors (TFs) such as Twist1 and Snail1 (Lim and Thiery, 2012 and Nieto, 2011).
    Cell Reports 01/2015; 338. DOI:10.1016/j.celrep.2014.12.032 · 7.21 Impact Factor
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    • "We previously reported that normal mammospheres can be passaged in suspension for a maximum of four passages, beyond which they fail to generate spheres and largely undergo senescence (Dey et al., 2009). 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. "
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    • "During chronic inflammation, tissues can become either fibrotic , exhibiting excessive synthesis and deposition of ECM, or cancerous , exhibiting again remodeled matrix and enhanced capacity for cell motility [3] [4]. Furthermore, EMT is thought to facilitate the extracellular microenvironment that fosters stem cell proliferation and maintenance in the context of cancer development [5]; EMT endows cancer cells with resistance to oncogene-induced senescence and chemo-or radiotherapeutic regimes, thus contributing to the generation and propagation of so-called cancer stem cells that are responsible for the long-term maintenance and metastatic dissemination of this disease [6] [7] [8]. Many of the key contributions of EMT in cancer progression Biochimica et Biophysica Acta 1840 (2014) 2621–2634 ☆ This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. "
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    ABSTRACT: Background The progression of cancer through stages that guide a benign hyperplastic epithelial tissue towards a fully malignant and metastatic carcinoma, is driven by genetic and microenvironmental factors that remodel the tissue architecture. The concept of epithelial-mesenchymal transition (EMT) has evolved to emphasize the importance of plastic changes in tissue architecture, and the cross-communication of tumor cells with various cells in the stroma and with specific molecules in the extracellular matrix (ECM). Scope of the review Among the multitude of ECM-embedded cytokines and the regulatory potential of ECM molecules, this article focuses on the cytokine transforming growth factor β (TGFβ) and the glycosaminoglycan hyaluronan, and their roles in cancer biology and EMT. For brevity, we concentrate our effort on breast cancer. Major conclusions Both normal and abnormal TGFβ signaling can be detected in carcinoma and stromal cells, and TGFβ-induced EMT requires the expression of hyaluronan synthase 2 (HAS2). Correspondingly, hyaluronan is a major constituent of tumor ECM and aberrant levels of both hyaluronan and TGFβ are thought to promote a wounding reaction to the local tissue homeostasis. The link between EMT and metastasis also involves the mesenchymal-epithelial transition (MET). ECM components, signaling networks, regulatory non-coding RNAs and epigenetic mechanisms form the network of regulation during EMT-MET. General significance Understanding the mechanism that control epithelial plasticity in the mammary gland promises the development of valuable biomarkers for the prognosis of breast cancer progression and even provides new ideas for a more integrative therapeutic approach against disease. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.
    Biochimica et Biophysica Acta (BBA) - General Subjects 08/2014; 1840(8). DOI:10.1016/j.bbagen.2014.02.004 · 3.83 Impact Factor
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