Cancer stem cells: A contentious hypothesis now moving forward

O'Connor, M. L.; Xiang, Dongxi; Shigdar, Sarah; Macdonald, Joanna; Yong, Li; Wang, Tao; Pu, Chunwen; Wang, Zhidong; Qiao, Liang; Duan, Wei

doi:10.1016/j.canlet.2013.11.012

Cited by 216 publications

(170 citation statements)

References 89 publications

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“…The CSC model is also involved in tumour heterogeneity 64,65 . Specifically, genetically distinct subclones together with developmental pathways and epigenetic modifications can contribute to functional heterogeneity and chemoresistance 65 .…”

Section: Cancer Stem Cellsmentioning

confidence: 99%

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Bañales

Cardinale

Carpino

et al. 2016

Nat Rev Gastroenterol Hepatol

1,105

1,139

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Section: Cancer Stem Cellsmentioning

confidence: 99%

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Bañales

Cardinale

Carpino

et al. 2016

Nat Rev Gastroenterol Hepatol

1,105

1,139

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“…These cells have also been termed "cancer stem cells," or "cancer-initiating cells," and can grow into tumorigenic, multicellular spheroids under low attachment conditions. Although the hierarchical model of TIC development may be dynamic, TICs do share many of the same features as normal stem cells including quiescence, resistance to chemotherapy, long-term self-renewal and ability to differentiate into various cell lineages 7,8 .…”

Section: Introductionmentioning

confidence: 99%

<em>In vitro</em> Enrichment of Ovarian Cancer Tumor-initiating Cells

House¹,

Hernandez²,

Annunziata³

2015

JoVE

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Evidence suggests that small subpopulations of tumor cells maintain a unique self-renewing and differentiation capacity and may be responsible for tumor initiation and/or relapse. Clarifying the mechanisms by which these tumor-initiating cells (TICs) support tumor formation and progression could lead to the development of clinically favorable therapies. Ovarian cancer is a heterogeneous and highly recurrent disease. Recent studies suggest TICs may play an important role in disease biology. We have identified culture conditions that enrich for TICs from ovarian cancer cell lines. Growing either adherent cells or non-adherent 'floater' cells in a low attachment plate with serum free media in the presence of growth factors supports the propagation of ovarian cancer TICs with stem cell markers (CD133 and ALDH activity) and increased tumorigenicity without the need to physically separate the TICs from other cell types within the culture. Although the presence of floater cells is not common for all cell lines, this population of cells with innate low adherence may have high tumorigenic potential.Compared to adherent cells grown in the presence of serum, TICs readily form spheres, are significantly more tumorigenic in mice, and express putative stem cell markers. The conditions are easy to establish in a timely manner and can be used to study signaling pathways important for maintaining stem characteristics, and to identify drugs or combinations of drugs targeting TICs. The culture conditions described herein are applicable for a variety of ovarian cancer cells of epithelial origin and will be critical in providing new information about the role of TICs in tumor initiation, progression, and relapse.

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“…22 However, in spite of these and other objections, the continued accumulation of experimental data provides increasing support for the CSC hypothesis. 17,[23][24][25][26][27][28] EPITHELIAL TO MESENCHYMAL TRANSITION During epithelial to mesenchymal transition (EMT), cells lose cellular adhesion and polarity and acquire an invasive phenotype. 29,30 EMT is associated with loss of E-cadherin and increased expression of other biomarkers including Snail, Slug, ZEB1, ZEB2 and N-cadherin (Figures 1 and 2; Table 2).…”

mentioning

confidence: 99%

The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors

Hardin

Zhang

Helein

et al. 2017

Laboratory Investigation

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The cancer stem-like cell (CSC) hypothesis postulates that a small population of cells in a cancer has self-renewal and clonal tumor initiation properties. These cells are responsible for tumor initiation, growth, recurrence and for resistance to chemotherapy and radiation therapy. CSCs can be characterized using markers such as SSEA-1, SSEA-4, CD44, CD24, ALDEFLUOR and others. CSCs form spheres when they are cultured in serum-free condition in low attachment plates and can generate tumors when injected into immune-deficient mice. During epithelial to mesenchymal transition (EMT), cells lose cellular adhesion and polarity and acquire an invasive phenotype. Recent studies have established a relationship between EMT and increased numbers of CSCs in some solid malignancies. Non-coding RNAs such as microRNAs and long non-coding RNAs (lncRNAs) have been shown to have important roles during EMT and some of these molecules also have regulatory roles in the proliferation of CSCs. Specific lncRNAs enhanced cell migration and invasion in breast carcinomas, which was associated with the generation of stem cell properties. The tumor microenvironment of CSCs also has an important role in tumor progression. Recent studies have shown that the interaction between tumor cells and the local microenvironment at the metastatic site leads to the development of premetastatic niche(s) and allows for the proliferation of the metastatic cells during colonization. The role of exosomes in the microenvironment during the EMT program is currently a major area of research. This review examines CSCs and the relationship between EMT and CSCs in solid tumors with emphasis on thyroid CSCs. The role of non-coding RNAs and of the microenvironment in EMT and in tumor progression are also examined. This review also highlights the growing number of studies that show the close association of EMT and CSCs and the role of exosomes and other elements of the tissue microenvironment in CSC metastasis. A better understanding of these mechanisms will lead to more effective targeting of primary and metastatic malignancies.

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Cancer stem cells: A contentious hypothesis now moving forward

Cited by 216 publications

References 89 publications

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

<em>In vitro</em> Enrichment of Ovarian Cancer Tumor-initiating Cells

The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors

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