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子宫内膜癌干细胞:癌症治疗的新靶点。

Endometrial cancer stem cells: a new target for cancer therapy.

机构信息

Department of Obstetrics and Gynecology, Faculty of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.

出版信息

Anticancer Res. 2012 Jun;32(6):2283-93.

PMID:22641664
Abstract

Adult stem cells have recently been identified in several types of mature tissue and it has also been suggested that stem-like cells exist in cancerous tissues. In this regard, stem-like cell subpopulations, referred to as side-population (SP) cells, have been identified in several tissue and tumor types, based on their ability to remove intracellular Hoechst 33342, a fluorescent dye. We have isolated and characterized SP cells from normal human endometrium and an endometrial cancer cell line. Endometrial SP cells can function as progenitor cells. Endometrial cancer SP cells possess the following characteristics: i) reduced expression levels of differentiation markers, ii) long-term repopulating properties, iii) self-renewal capacity, iv) enhanced migration and podia formation, v) enhanced tumorigenicity, and vi) bi-potential development (tumor cells and stroma-like cells), suggesting that they have cancer stem-like cell features. Recently, we demonstrated that sodium butyrate, a histone deacetylase (HDAC) inhibitor, inhibited the self-renewal capacity of endometrial cancer SP cells by inducing a DNA damage response. Here, we review recent articles that show the presence of stem cells in normal endometrium and endometrial cancer and introduce the results of our own recent studies.

摘要

成人干细胞最近在几种成熟组织中被发现,也有人提出,在癌组织中存在类似干细胞的细胞。在这方面,基于其去除细胞内 Hoechst 33342(一种荧光染料)的能力,已在几种组织和肿瘤类型中鉴定出称为侧群 (SP) 细胞的类似干细胞的细胞亚群。我们已经从正常人类子宫内膜和子宫内膜癌细胞系中分离和表征了 SP 细胞。子宫内膜 SP 细胞可以作为祖细胞发挥功能。子宫内膜癌 SP 细胞具有以下特征:i)分化标志物表达水平降低,ii)长期重编程特性,iii)自我更新能力,iv)增强的迁移和伪足形成,v)增强的致瘤性,以及 vi)双潜能发育(肿瘤细胞和基质样细胞),表明它们具有类似癌症干细胞的特征。最近,我们证明了组蛋白去乙酰化酶 (HDAC) 抑制剂丁酸钠通过诱导 DNA 损伤反应抑制子宫内膜癌 SP 细胞的自我更新能力。在这里,我们回顾了最近的文章,这些文章表明在正常子宫内膜和子宫内膜癌中存在干细胞,并介绍了我们自己最近的研究结果。

相似文献

1
Endometrial cancer stem cells: a new target for cancer therapy.子宫内膜癌干细胞:癌症治疗的新靶点。
Anticancer Res. 2012 Jun;32(6):2283-93.
2
Stem cells in human normal endometrium and endometrial cancer cells: characterization of side population cells.人正常子宫内膜和子宫内膜癌细胞中的干细胞:侧群细胞的特征。
Kaohsiung J Med Sci. 2012 Feb;28(2):63-71. doi: 10.1016/j.kjms.2011.06.028. Epub 2012 Jan 25.
3
Stem cells in endometrium and endometrial cancer: accumulating evidence and unresolved questions.子宫内膜和子宫内膜癌中的干细胞:不断增加的证据和未解决的问题。
Cancer Lett. 2011 Sep 28;308(2):123-33. doi: 10.1016/j.canlet.2011.05.015. Epub 2011 Jun 17.
4
Sodium butyrate inhibits the self-renewal capacity of endometrial tumor side-population cells by inducing a DNA damage response.丁酸钠通过诱导 DNA 损伤反应抑制子宫内膜肿瘤侧群细胞的自我更新能力。
Mol Cancer Ther. 2011 Aug;10(8):1430-9. doi: 10.1158/1535-7163.MCT-10-1062. Epub 2011 Jun 1.
5
Characterization of side-population cells in human normal endometrium.人正常子宫内膜中侧群细胞的鉴定
Hum Reprod. 2007 May;22(5):1214-23. doi: 10.1093/humrep/del514. Epub 2007 Feb 5.
6
The inhibitory effect of salinomycin on the proliferation, migration and invasion of human endometrial cancer stem-like cells.沙利霉素对人子宫内膜癌干细胞样细胞增殖、迁移和侵袭的抑制作用。
Gynecol Oncol. 2013 Jun;129(3):598-605. doi: 10.1016/j.ygyno.2013.03.005. Epub 2013 Mar 13.
7
Stem cells in human endometrium and endometrial carcinoma.人子宫内膜和子宫内膜癌中的干细胞。
Int J Gynecol Pathol. 2011 Jul;30(4):317-27. doi: 10.1097/PGP.0b013e3182102754.
8
Endometrial Cancer Stem Cell as a Potential Therapeutic Target.子宫内膜癌干细胞作为一种潜在的治疗靶点。
Semin Reprod Med. 2015 Sep;33(5):341-9. doi: 10.1055/s-0035-1563407. Epub 2015 Aug 18.
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SPARC was overexpressed in human endometrial cancer stem-like cells and promoted migration activity.富含半胱氨酸的酸性分泌蛋白(SPARC)在人子宫内膜癌干细胞样细胞中过表达,并促进迁移活性。
Gynecol Oncol. 2014 Aug;134(2):356-63. doi: 10.1016/j.ygyno.2014.04.009. Epub 2014 Apr 25.
10
Evidence for cancer stem cells in human endometrial carcinoma.人类子宫内膜癌中癌症干细胞的证据。
Cancer Res. 2009 Nov 1;69(21):8241-8. doi: 10.1158/0008-5472.CAN-08-4808. Epub 2009 Oct 20.

引用本文的文献

1
Butyrate enhances gut dysbiosis by activating the cAMP/PKA/CREB signaling pathway to inhibit the progression of endometrial carcinoma.丁酸盐通过激活cAMP/PKA/CREB信号通路增强肠道菌群失调,从而抑制子宫内膜癌的进展。
BMC Microbiol. 2025 Aug 16;25(1):516. doi: 10.1186/s12866-025-04190-2.
2
The Prognostic Role and Significance of Dll4 and Toll-like Receptors in Cancer Development.Dll4和Toll样受体在癌症发展中的预后作用及意义
Cancers (Basel). 2022 Mar 24;14(7):1649. doi: 10.3390/cancers14071649.
3
Histone Deacetylase Inhibitors: A Promising Therapeutic Alternative for Endometrial Carcinoma.
组蛋白去乙酰化酶抑制剂:子宫内膜癌有前途的治疗选择。
Dis Markers. 2021 Nov 12;2021:7850688. doi: 10.1155/2021/7850688. eCollection 2021.
4
Exploring lncRNA-Mediated Regulatory Networks in Endometrial Cancer Cells and the Tumor Microenvironment: Advances and Challenges.探索子宫内膜癌细胞和肿瘤微环境中lncRNA介导的调控网络:进展与挑战
Cancers (Basel). 2019 Feb 16;11(2):234. doi: 10.3390/cancers11020234.
5
Immunohistochemical expression of hormone receptors, Ki-67, endoglin (CD105), claudins 3 and 4, MMP-2 and -9 in endometrial polyps and endometrial cancer type I.激素受体、Ki-67、内皮糖蛋白(CD105)、紧密连接蛋白3和4、基质金属蛋白酶-2和-9在子宫内膜息肉和Ⅰ型子宫内膜癌中的免疫组化表达
Onco Targets Ther. 2018 Jul 9;11:3949-3958. doi: 10.2147/OTT.S160014. eCollection 2018.
6
CHD4 mutations promote endometrial cancer stemness by activating TGF-beta signaling.CHD4突变通过激活转化生长因子-β信号通路促进子宫内膜癌干性。
Am J Cancer Res. 2018 May 1;8(5):903-914. eCollection 2018.
7
DPPIV promotes endometrial carcinoma cell proliferation, invasion and tumorigenesis.二肽基肽酶IV促进子宫内膜癌细胞的增殖、侵袭和肿瘤发生。
Oncotarget. 2017 Jan 31;8(5):8679-8692. doi: 10.18632/oncotarget.14412.
8
Molecular cues on obesity signals, tumor markers and endometrial cancer.肥胖信号、肿瘤标志物与子宫内膜癌的分子线索。
Horm Mol Biol Clin Investig. 2015 Jan;21(1):89-106. doi: 10.1515/hmbci-2014-0049.
9
Emerging therapeutic biomarkers in endometrial cancer.子宫内膜癌的新兴治疗性生物标志物。
Biomed Res Int. 2013;2013:130362. doi: 10.1155/2013/130362. Epub 2013 Jun 11.