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脑肿瘤干细胞。

Brain cancer stem cells.

机构信息

Department of Biosciences and Biotechnology, University of Milan Bicocca, Piazza della Scienza 2, Building U3, 20126 Milan, Italy.

出版信息

J Mol Med (Berl). 2009 Nov;87(11):1087-95. doi: 10.1007/s00109-009-0535-3. Epub 2009 Sep 29.

DOI:10.1007/s00109-009-0535-3
PMID:19784875
Abstract

Cancers comprise heterogeneous cells, ranging from highly proliferative immature precursors to more differentiated cell lineages. In the last decade, several groups have demonstrated the existence of cancer stem cells in both nonsolid solid tumors, including some of the brain: glioblastoma multiforme (GBM), medulloblastoma, and ependymoma. These cells, like their normal counterpart in homologous tissues, are multipotent, undifferentiated, self-sustaining, yet transformed cells. In particular, glioblastoma-stem like cells (GBSCs) self-renew under clonal conditions and differentiate into neuron- and glia-like cells, with aberrant, mixed neuronal/astroglial phenotypes. Remarkably, upon subcutaneous and intracerebral transplantation in immunosuppressed mice, GBSCs are able to form secondary tumors that closely resemble the human pathology, a property retained also throughout serial transplantation. The search is up for the identification of the markers and the molecular mechanisms that underpin the tumorigenic potential of these cells. This is critical if we aim at defining new therapeutic approaches for the treatment of malignant brain tumors. Lately, it has been shown that some key regulatory system that plays pivotal roles in neural stem cell physiology can also regulate the tumorigenic ability of cancer stem cells in GBMs. This suggests that the study of cancer stem cells in brain tumors might help to identify new and more specific therapeutic molecular effectors, with the cancer stem cells themselves representing one of the main targets, in fact the Holy Grail, in cancer cell therapy. This review includes a summary review on brain cancer cells and their usefulness as emerging targets in cancer cell therapy.

摘要

癌症由异质性细胞组成,范围从高度增殖的不成熟前体细胞到更分化的细胞谱系。在过去的十年中,有几个小组已经证明了癌症干细胞在包括大脑在内的实体肿瘤中的存在:多形性胶质母细胞瘤(GBM)、髓母细胞瘤和室管膜瘤。这些细胞与同源组织中的正常细胞一样,具有多能性、未分化性、自我维持性,但具有转化性。特别是,胶质母细胞瘤样细胞(GBSCs)在克隆条件下自我更新,并分化为神经元和神经胶质样细胞,具有异常的、混合的神经元/星形胶质细胞表型。值得注意的是,在免疫抑制小鼠的皮下和脑内移植后,GBSCs 能够形成与人类病理非常相似的次级肿瘤,这种特性在连续移植中也得以保留。人们正在寻找鉴定这些细胞的标志物和分子机制,这些标志物和分子机制是这些细胞肿瘤发生潜力的基础。如果我们旨在确定治疗恶性脑肿瘤的新治疗方法,这一点至关重要。最近已经表明,在神经干细胞生理学中发挥关键作用的一些关键调节系统也可以调节 GBM 中癌症干细胞的肿瘤发生能力。这表明研究脑肿瘤中的癌症干细胞可能有助于确定新的、更特异的治疗性分子效应物,而癌症干细胞本身就是癌症细胞治疗的主要靶点之一,实际上是圣杯。这篇综述包括对脑癌细胞及其作为癌症细胞治疗中新兴靶点的有用性的综述。

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Brain cancer stem cells.脑肿瘤干细胞。
J Mol Med (Berl). 2009 Nov;87(11):1087-95. doi: 10.1007/s00109-009-0535-3. Epub 2009 Sep 29.
2
Brain tumour stem cells: possibilities of new therapeutic strategies.脑肿瘤干细胞:新治疗策略的可能性
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Mouse induced glioma-initiating cell models and therapeutic targets.鼠诱导的神经胶质瘤起始细胞模型和治疗靶点。
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Distinct pools of cancer stem-like cells coexist within human glioblastomas and display different tumorigenicity and independent genomic evolution.不同的癌症干细胞样细胞群共存于人类胶质母细胞瘤中,并表现出不同的致瘤性和独立的基因组进化。
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本文引用的文献

1
The increasing complexity of the cancer stem cell paradigm.癌症干细胞模式日益复杂。
Science. 2009 Jun 26;324(5935):1670-3. doi: 10.1126/science.1171837.
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Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells.缺氧诱导因子调节胶质瘤干细胞的致瘤能力。
Cancer Cell. 2009 Jun 2;15(6):501-13. doi: 10.1016/j.ccr.2009.03.018.
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SSEA-1 is an enrichment marker for tumor-initiating cells in human glioblastoma.SSEA-1是人类胶质母细胞瘤中肿瘤起始细胞的富集标志物。
Cell Transplant. 2022 Jan-Dec;31:9636897221102903. doi: 10.1177/09636897221102903.
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Disulfiram and copper combination therapy targets NPL4, cancer stem cells and extends survival in a medulloblastoma model.双硫仑和铜联合治疗针对 NPL4、癌症干细胞,并延长髓母细胞瘤模型中的存活时间。
PLoS One. 2021 Nov 3;16(11):e0251957. doi: 10.1371/journal.pone.0251957. eCollection 2021.
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Glioma Stem Cells as Immunotherapeutic Targets: Advancements and Challenges.作为免疫治疗靶点的胶质瘤干细胞:进展与挑战
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Autophagy in cancers including brain tumors: role of MicroRNAs.自噬在包括脑肿瘤在内的癌症中的作用:MicroRNAs 的作用。
Cell Commun Signal. 2020 Jun 9;18(1):88. doi: 10.1186/s12964-020-00587-w.
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Targeting the Sphingolipid System as a Therapeutic Direction for Glioblastoma.靶向鞘脂系统作为胶质母细胞瘤的治疗方向
Cancers (Basel). 2020 Jan 1;12(1):111. doi: 10.3390/cancers12010111.
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Knockdown of long non-coding RNA PCAT1 in glioma stem cells promotes radiation sensitivity.敲低胶质瘤干细胞中的长链非编码RNA PCAT1可提高辐射敏感性。
Med Mol Morphol. 2019 Jun;52(2):114-122. doi: 10.1007/s00795-018-0209-8. Epub 2018 Dec 18.
9
The embryonic type of SPP1 transcriptional regulation is re-activated in glioblastoma.SPP1转录调控的胚胎型在胶质母细胞瘤中被重新激活。
Oncotarget. 2017 Mar 7;8(10):16340-16355. doi: 10.18632/oncotarget.14092.
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Multidrug-resistant cancer cells and cancer stem cells hijack cellular systems to circumvent systemic therapies, can natural products reverse this?耐多药癌细胞和癌症干细胞会利用细胞系统来规避全身治疗,天然产物能逆转这种情况吗?
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The receptor interacting protein 1 inhibits p53 induction through NF-kappaB activation and confers a worse prognosis in glioblastoma.受体相互作用蛋白1通过激活核因子κB抑制p53诱导,并在胶质母细胞瘤中预示更差的预后。
Cancer Res. 2009 Apr 1;69(7):2809-16. doi: 10.1158/0008-5472.CAN-08-4079.
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Distinct pools of cancer stem-like cells coexist within human glioblastomas and display different tumorigenicity and independent genomic evolution.不同的癌症干细胞样细胞群共存于人类胶质母细胞瘤中,并表现出不同的致瘤性和独立的基因组进化。
Oncogene. 2009 Apr 16;28(15):1807-11. doi: 10.1038/onc.2009.27. Epub 2009 Mar 16.
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Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy.工程化人骨髓间充质干细胞用于癌症治疗的疗效评估及转归
Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4822-7. doi: 10.1073/pnas.0806647106. Epub 2009 Mar 5.
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In vivo imaging, tracking, and targeting of cancer stem cells.癌症干细胞的体内成像、追踪与靶向
J Natl Cancer Inst. 2009 Mar 4;101(5):350-9. doi: 10.1093/jnci/djn509. Epub 2009 Feb 24.
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Inhibition of Akt inhibits growth of glioblastoma and glioblastoma stem-like cells.抑制Akt可抑制胶质母细胞瘤和胶质母细胞瘤干细胞样细胞的生长。
Mol Cancer Ther. 2009 Feb;8(2):386-93. doi: 10.1158/1535-7163.MCT-08-0680. Epub 2009 Feb 10.
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Different response of human glioma tumor-initiating cells to epidermal growth factor receptor kinase inhibitors.人类胶质瘤肿瘤起始细胞对表皮生长因子受体激酶抑制剂的不同反应。
J Biol Chem. 2009 Mar 13;284(11):7138-48. doi: 10.1074/jbc.M807111200. Epub 2009 Jan 14.
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Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model.在一种体细胞肿瘤抑制小鼠模型中,恶性星形细胞瘤起源于神经干细胞/祖细胞。
Cancer Cell. 2009 Jan 6;15(1):45-56. doi: 10.1016/j.ccr.2008.12.006.