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[肿瘤干细胞假说对理解卵巢癌的重要性]

[Importance of the tumor stem cell hypothesis for understanding ovarian cancer].

作者信息

Vochem R, Einenkel J, Horn L-C, Ruschpler P

机构信息

Zentrum für Frauen- und Kindermedizin, Gynäkologische Onkologie, Universitätsfrauenklinik Leipzig, Liebigstr. 20a, 04103, Leipzig, Deutschland.

出版信息

Pathologe. 2014 Jul;35(4):361-70. doi: 10.1007/s00292-014-1910-6.

DOI:10.1007/s00292-014-1910-6
PMID:24992976
Abstract

BACKGROUND

Despite complex surgical and systemic therapies epithelial ovarian cancer has a poor prognosis. A small quantity of tumorigenic cells termed cancer stem cells (CSC) are responsible for the development of chemoresistance and high rates of recurrence.

OBJECTIVES

This review presents the CSC hypothesis and describes methods of identification and enrichment of CSCs as well as approaches for the therapeutic use of these findings.

MATERIAL AND METHODS

A systematic literature review based on PubMed and Web of Science was carried out.

RESULTS

The CSC model is based on a hierarchical structure of tumors with few CSCs and variably differentiated tumor cells constituting the tumor bulk. Only the CSCs possess tumorigenic potential. Other essential functional characteristics of CSCs are their potential for self-renewal and their ability to differentiate into further cell types. The CSCs are structurally characterized by different surface markers and changes in certain signaling pathways. Currently there are phase I and II studies in progress investigating specific influences on CSCs.

CONCLUSION

Various clinical characteristics of the course of disease in ovarian cancer are aptly represented by the tumor stem cell model. In spite of precisely defined functional characteristics of CSCs, surface markers and signaling pathways show individual differences and vary between tumor entities. This complicates identification and enrichment. Current experimental findings in various approaches and even first clinical studies raise hopes for a personalized cancer therapy targeting CSCs.

摘要

背景

尽管采用了复杂的手术和全身治疗方法,上皮性卵巢癌的预后仍然很差。少量具有致瘤性的细胞,即癌症干细胞(CSC),是导致化疗耐药和高复发率的原因。

目的

本综述介绍了癌症干细胞假说,描述了癌症干细胞的鉴定和富集方法,以及这些研究结果在治疗中的应用方法。

材料与方法

基于PubMed和Web of Science进行了系统的文献综述。

结果

癌症干细胞模型基于肿瘤的分层结构,其中少量癌症干细胞和分化程度不同的肿瘤细胞构成肿瘤主体。只有癌症干细胞具有致瘤潜力。癌症干细胞的其他重要功能特征是其自我更新潜力和分化为其他细胞类型的能力。癌症干细胞在结构上的特征是具有不同的表面标志物和某些信号通路的变化。目前正在进行一期和二期研究,以调查对癌症干细胞的特定影响。

结论

肿瘤干细胞模型恰当地体现了卵巢癌病程的各种临床特征。尽管癌症干细胞的功能特征、表面标志物和信号通路有明确的定义,但它们存在个体差异,并且在不同肿瘤实体之间也有所不同。这使得鉴定和富集变得复杂。目前各种方法的实验结果甚至初步临床研究都为针对癌症干细胞的个性化癌症治疗带来了希望。

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引用本文的文献

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J Ovarian Res. 2016 Mar 3;9:12. doi: 10.1186/s13048-016-0221-3.

本文引用的文献

1
Stem cells' guided gene therapy of cancer: New frontier in personalized and targeted therapy.干细胞导向性癌症基因治疗:个性化与靶向治疗的新前沿。
J Cancer Res Ther (Manch). 2014;2(1):22-33. doi: 10.14312/2052-4994.2014-4.
2
Ovarian cancer spheroid cells with stem cell-like properties contribute to tumor generation, metastasis and chemotherapy resistance through hypoxia-resistant metabolism.具有干细胞样特性的卵巢癌细胞球体通过耐缺氧代谢促进肿瘤发生、转移和化疗耐药。
PLoS One. 2014 Jan 7;9(1):e84941. doi: 10.1371/journal.pone.0084941. eCollection 2014.
3
Ovarian cancer stem cells: are they real and why are they important?
卵巢癌干细胞:它们是否真实存在,为什么它们很重要?
Gynecol Oncol. 2014 Feb;132(2):483-9. doi: 10.1016/j.ygyno.2013.12.001. Epub 2013 Dec 7.
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Unravelling cancer stem cell potential.解析癌症干细胞潜能。
Nat Rev Cancer. 2013 Oct;13(10):727-38. doi: 10.1038/nrc3597.
5
The stem-cell profile of ovarian surface epithelium is reproduced in the oviductal fimbriae, with increased stem-cell marker density in distal parts of the fimbriae.卵巢表面上皮的干细胞特征在输卵管伞中重现,在伞的远端干细胞标志物密度增加。
Int J Gynecol Pathol. 2013 Sep;32(5):444-53. doi: 10.1097/PGP.0b013e3182800ad5.
6
SOX2 expression associates with stem cell state in human ovarian carcinoma.SOX2 表达与人卵巢癌细胞的干细胞状态相关。
Cancer Res. 2013 Sep 1;73(17):5544-55. doi: 10.1158/0008-5472.CAN-12-4177. Epub 2013 Jul 18.
7
Ovarian surface epithelium as a source of ovarian cancers: unwarranted speculation or evidence-based hypothesis?卵巢表面上皮作为卵巢癌的来源:毫无根据的推测还是基于证据的假说?
Gynecol Oncol. 2013 Jul;130(1):246-51. doi: 10.1016/j.ygyno.2013.03.021. Epub 2013 Apr 2.
8
Cancer genome landscapes.肿瘤基因组图谱。
Science. 2013 Mar 29;339(6127):1546-58. doi: 10.1126/science.1235122.
9
Precursors and pathogenesis of ovarian carcinoma.卵巢癌的发生前驱和发病机制。
Pathology. 2013 Apr;45(3):229-42. doi: 10.1097/PAT.0b013e32835f2264.
10
Fallopian tube precursors of ovarian low- and high-grade serous neoplasms.卵巢低级别和高级别浆液性肿瘤的输卵管前体。
Histopathology. 2013 Jan;62(1):44-58. doi: 10.1111/his.12046.