Characterization of side-population cells in human normal endometrium

Kato, Kanefusa; Yoshimoto, Momoko; Kato, Kuniki; Adachi, Shun; Yamayoshi, Asako; Arima, Takahiro; Asanoma, Kazuo; Kyo, Satoru; Nakahata, Tatsutoshi; Wake, Norio

doi:10.1093/humrep/del514

Cited by 215 publications

(207 citation statements)

References 27 publications

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“…Still, others have identified SP cells in benign endometrium. 31 Interestingly, while the SP fraction was enriched in the CD9 -, CD13 -cell sub-population, the SP cells could give rise to CD9 + gland-like cells and CD13 + stromal cells. 31 It is not clear, however, whether or not there are multiple classes/gradations of stem/progenitor cells that can give rise to the glandular epithelium and stromal cells.…”

Section: Discussionmentioning

confidence: 95%

“…Data from a more recent study that identified SP and non-SP populations in benign endometrium suggests that stem/progenitor endometrial cells may give rise to both epithelial and stromal cells 31 and implicates a more endogenous source. We assessed the cellular phenotype of cells derived from a serially transplanted tumor by flow cytometry analysis of the expression of Ep-CAM, an epithelial marker.…”

Section: Resultsmentioning

confidence: 99%

“…31 It is not clear, however, whether or not there are multiple classes/gradations of stem/progenitor cells that can give rise to the glandular epithelium and stromal cells. 31,42 In contrast to this concept there are those who have provided evidence to suggest the bone marrow cells can give rise to endometrial cells 30,43 inferring that the bone marrow may harbor a stem cell that has the potential to become an endometrial cell whether it be epithelial or stromal.…”

Section: Discussionmentioning

confidence: 99%

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Functional analyses of the cancer stem cell-like properties of human endometrial tumor initiating cells

Friel¹,

Sergent²,

Patnaude³

et al. 2008

Cell Cycle

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Recent data suggest that rare stem cell populations with the capacity to self renew and drive tumor formation are a feature of solid tumors. Several investigators have identified putative stem cells from solid tumors and cancer cell lines following isolation of a side population (SP) defined by dye exclusion. We investigated this parameter in our efforts to identify an endometrial cancer (EnCa) stem cell population. Multiple EnCa cell lines were assessed and verapamil sensitive SP and non-SP cells were isolated from two human EnCa cell lines. The functional significance of the SP and non-SP derived from AN3CA was evaluated in vitro and in vivo. SP cells proliferated at a significantly slower rate than the non-SP fraction, and a larger proportion of the SP cells were in the G 1 phase of the cell cycle as compared to the non-SP fraction. The SP fraction was more resistant to the chemotherapeutic agent paclitaxel. The SP comprised ~0.02% of the initial AN3CA cell population and this proportion of SP cells was maintained within the larger heterogeneous population following repeated passages of purified SP cells. These findings suggest that SP cells derived from the AN3CA cell line have the stem cell properties of low proliferative activity, chemoresistance and self-renewal. We also tested relative tumor formation activity of the SP and non-SP fractions. Only the SP fraction was tumorigenic. Additionally, we identified SP fractions in primary EnCa. Together these results are consistent with the hypothesis that EnCa contain a subpopulation of tumor initiating cells with stem like properties.

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Section: Discussionmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Functional analyses of the cancer stem cell-like properties of human endometrial tumor initiating cells

Friel¹,

Sergent²,

Patnaude³

et al. 2008

Cell Cycle

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“…Cell subpopulations with the features of stem cells have been detected in a number of mammalian species, including humans, using the fluorescent stain Hoechst 33342 and these minor populations are termed side population (SP) cells (Goodell et al 1996). Further, Kato et al (2007) have isolated such cells from human endometrium and showed that they can be categorized as progenitor cells because they can differentiate into epithelial and stromal endometrial cells. Cervello et al described a population of label-retaining cells (LRCs) in mouse endometrium which express markers specific for undifferentiated cells -c-kit and pou5f1 (Chan & Gargett 2006, Cervello et al 2007.…”

Section: Introductionmentioning

confidence: 99%

Characterization of clonogenic stromal cells isolated from human endometrium

Dimitrov¹,

Timeva²,

Kyurkchiev³

et al. 2008

Reproduction

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104

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Human endometrium is an object of extensive restructuring and remodeling during the female reproductive life and it is quite tempting to assume that these periodic changes happen with the participation of cells that should have the basic characteristics of multipotent cells. The aim of this study was to search for the presence of cells with plastic adherence, clonogenicity, and differentiation in human endometrium. To this end, human endometrial stromal cells were cultured in vitro for more than 15 passages. Flow cytometry analysis of the cultured cells showed that they were positive for CD29, CD73 and CD90, which are considered to be the markers of cells with mesenchymal origin. The cells were negative for the hematopoietic cell markers (CD45, CD34, CD14, CD3, CD19, CD16/56, and HLA-DR). Further, it was shown that the cultured cells had 15% clonogenic efficiency and could be induced to differentiate into adipogenic cells containing typical lipid-rich vacuoles. These results demonstrate that the human endometrium contains a low number of cells with the characteristics of endometrial stromal stem/progenitor cells, which seem to belong to the family of the mesenchymal stem cells. It can be speculated that these cells are engaged into the monthly restructuring and remodeling of human endometrium.Reproduction (2008) 135 551-558

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“…We have isolated SP cells from normal human endometrium and from a human endometrial cancer cell line, Hec1, and characterized their properties (28,29). We have shown that Hec1-SP cells have cancer stem-like cell features.…”

Section: Introductionmentioning

confidence: 99%

Sodium Butyrate Inhibits the Self-Renewal Capacity of Endometrial Tumor Side-Population Cells by Inducing a DNA Damage Response

Kato

Kuhara

Yoneda

et al. 2011

Molecular Cancer Therapeutics

Self Cite

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We previously isolated side-population (SP) cells from a human endometrial cancer cell line, Hec1, and determined that Hec1-SP cells have cancer stem-like cell features. In this study, we isolated SP cells and non-SP (NSP) cells derived from a rat endometrial cell line expressing human [ 12 Val] KRAS (RK12V cells) and determined the SP phenotype. RK12V-SP cells showed self-renewal capacity, the potential to develop into stromal cells, reduced expression levels of differentiation markers, long-term proliferating capacity in cultures, and enhanced tumorigenicity, indicating that RK12V-SP cells have cancer stem-like cell features. RK12V-SP cells also display higher resistance to conventional chemotherapeutic drugs. In contrast, treatment with a histone deacetylases (HDAC) inhibitor, sodium butyrate (NaB), reduced self-renewal capacity and completely suppressed colony formation of RK12V-SP cells in a soft agar. The levels of intracellular reactive oxygen species (ROS) and the number of gH2AX foci were increased by NaB treatment of both RK12V-SP cells and RK12V-NSP cells. The expression levels of gH2AX, p21, p27, and phospho-p38 mitogen-activated protein kinase were enhanced in RK12V-SP cells compared with RK12V-NSP cells. These results imply that treatment with NaB induced production of intracellular ROS and DNA damage in both RK12V-SP and RK12V-NSP cells. Following NaB treatment, DNA damage response signals were enhanced more in RK12V-SP cells than in RK12V-NSP cells. This is the first article on an inhibitory effect of NaB on proliferation of endometrial cancer stem-like cells. HDAC inhibitors may represent an attractive antitumor therapy based upon their inhibitory effects on cancer stem-like cells.

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Characterization of side-population cells in human normal endometrium

Cited by 215 publications

References 27 publications

Functional analyses of the cancer stem cell-like properties of human endometrial tumor initiating cells

Functional analyses of the cancer stem cell-like properties of human endometrial tumor initiating cells

Characterization of clonogenic stromal cells isolated from human endometrium

Sodium Butyrate Inhibits the Self-Renewal Capacity of Endometrial Tumor Side-Population Cells by Inducing a DNA Damage Response

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