Isolation and Molecular Characterization of Cancer Stem Cells in MMTV-<i>Wnt-1</i> Murine Breast Tumors

Cho, Robert W.; Wang, Xinhao; Diehn, Maximilian; Shedden, Kerby; Chen, Grace Y.; Sherlock, Gavin; Gurney, Austin; Lewicki, John; Clarke, Michael F.

doi:10.1634/stemcells.2007-0440

Cited by 265 publications

(262 citation statements)

References 49 publications

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“…Breast CSCs were also identified in MMTV-Wnt1 mice by the expression of CD24 and Thy1 (Thy1 has been used as a stem cell marker in other tissues and organs). When profiled, these cells produced a signature that was similar to published MaSC gene expression signatures [76]. Other global gene expression profiling analyses suggested that the mouse MaSC signature correlated with not only the MMTV-Wnt1 tumors, but also p53 -/-tumors [28].…”

Section: Much Of This Evidence Fits Into the Paradigm Of Tumorinitiatsupporting

confidence: 59%

From milk to malignancy: the role of mammary stem cells in development, pregnancy and breast cancer

Tiede

Kang

2011

Cell Res

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Adult stem cells of the mammary gland (MaSCs) are a highly dynamic population of cells that are responsible for the generation of the gland during puberty and its expansion during pregnancy. In recent years significant advances have been made in understanding how these cells are regulated during these developmentally important processes both in humans and in mice. Understanding how MaSCs are regulated is becoming a particularly important area of research, given that they may be particularly susceptible targets for transformation in breast cancer. Here, we summarize the identification of MaSCs, how they are regulated and the evidence for their serving as the origins of breast cancer. In particular, we focus on how changes in MaSC populations may explain both the increased risk of developing aggressive ER/PR(−) breast cancer shortly after pregnancy and the long-term decreased risk of developing ER/ PR(+) tumors.

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Section: Much Of This Evidence Fits Into the Paradigm Of Tumorinitiatsupporting

confidence: 59%

From milk to malignancy: the role of mammary stem cells in development, pregnancy and breast cancer

Tiede

Kang

2011

Cell Res

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“…The number of cells that are terminally differentiated is increasing over time, reaching a steady level that is comparable to normal growth, see Figure 6. Note that in both normal and benign tumor cases, the total stem cell population consisting of quiescent and progenitor populations is 5%, which is in agreement with experimental values, see [1], [4], [10].…”

Section: Disease Progression and Model Predictionssupporting

confidence: 89%

Modeling the Cancer Stem Cell Hypothesis

Calmelet

Prokop

Mensah

et al. 2010

Math. Model. Nat. Phenom.

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Abstract. Solid tumors and hematological cancers contain small population of tumor cells that are believed to play a critical role in the development and progression of the disease. These cells, named Cancer Stem Cells (CSCs), have been found in leukemia, myeloma, breast, prostate, pancreas, colon, brain and lung cancers. It is also thought that CSCs drive the metastatic spread of cancer. The CSC compartment features a specific and phenotypically defined cell population characterized with self-renewal (through mutations), quiescence or slow cycling, overexpression of anti-apoptotic proteins, multidrug resistance and impaired differentiation. CSCs show resistance to a number of conventional therapies, and it is believed that this explains why it is difficult to completely eradicate the disease and why recurrence is an ever-present threat. A hierarchical phenomenological model is proposed based on eight compartments following the stem cell lineage at the normal and cancer cell levels. As an empirical test, the tumor grading and progression, typically collected in the pathologic lab, is used to correlate the outcome of this model with the tumor development stages. In addition, the model is able to quantitatively account for the temporal development of the population of observed cell types. Two types of therapeutic treatment models are considered, with dose-density chemotherapy (a pulsatile scenario) as well as continuous, metronomic delivery. The drug hit is considered at the stem cell progenitor and early differentiated specialized cell levels for both normal and cancer cells, while the quiescent stem cell and fully differentiated compartments are considered favorable outcome for cancer treatment. Circulating progenitors are neglected in this analysis. The model provides a number of experimentally testable predictions. The relative importance of the cell kill and survival is demonstrated through a deterministic parametric study. The significance of the stem cell compartment is underlined based on this simulation study. This predictive mathematical model for cancer stem cell hypothesis is used

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“…In breast cancer, Cho et al (39) showed that cells displaying the CD90 1 /CD24 1 /CD49f 1 /CD45 2 immunophenotype, identified in MMTV-wnt-1 murine breast tumors, were highly enriched for cells, which were able to form tumors when transplanted into syngeneic recipients. In humans, Donnenberg et al (40) demonstrated that breast tumors contain a small population of CD44 1 /CD90 1 localized at the tumor periphery, adjacent to the CD90 1 stroma.…”

Section: Discussionmentioning

confidence: 99%

Differential expression of CD90 and CD14 stem cell markers in malignant breast cancer cell lines

et al. 2012

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The recently emerged concept of cancer stem cell (CSC) has led to a new hypothesis on the basis for tumor progression. Basically, the CSC theory hypothesizes the presence of a hierarchically organized and relatively rare cell population, which is responsible for tumor initiation, self-renewal, and maintenance, in addition to accumulation of mutation and resistance to chemotherapy. CSCs have recently been described in breast cancer. Different genetic markers have been used to isolate breast CSCs, none of which have been correlated with the tumorigenicity or metastatic potential of the cells, limiting their precise characterization and clinical application in the development of therapeutic protocols. Here, we sought for subpopulations of CSCs by analyzing 10 judiciously chosen stem cell markers in a normal breast cell line (MCF10-A) and in four human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-435, and Hs578-T) displaying different degrees of metastatic and invasiveness potential. We were able to identify two markers, which are differentially expressed in nontumorigenic versus tumor cells. The CD90 marker was highly expressed in the malignant cell lines. Interestingly, the CD14 molecule displayed higher expression levels in the nontumorigenic cell line. Therefore, we demonstrated that these two markers, which are more commonly used to isolate and characterize stem cells, are differentially expressed in breast tumor cells, when compared with nontumorigenic breast cells. ' 2012 International Society for Advancement of Cytometry Key terms CD90; Thy-1; breast cancer; cancer stem cell; CD14; breast cancer stem cell

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Isolation and Molecular Characterization of Cancer Stem Cells in MMTV-Wnt-1 Murine Breast Tumors

Cited by 265 publications

References 49 publications

From milk to malignancy: the role of mammary stem cells in development, pregnancy and breast cancer

From milk to malignancy: the role of mammary stem cells in development, pregnancy and breast cancer

Modeling the Cancer Stem Cell Hypothesis

Differential expression of CD90 and CD14 stem cell markers in malignant breast cancer cell lines

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