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正常干细胞和癌症干细胞发育阶段的趋同:对差异化治疗的启示。

Convergence of normal stem cell and cancer stem cell developmental stage: Implication for differential therapies.

机构信息

Shengwen Calvin Li, Katherine L Lee, William G Loudon, Neuro-Oncology Research Laboratory, Center for Neuroscience and Stem Cell Research, Children's Hospital of Orange County, University of California Irvine, 455 South Main Street, Orange, CA 92868, United States.

出版信息

World J Stem Cells. 2011 Sep 26;3(9):83-8. doi: 10.4252/wjsc.v3.i9.83.

Abstract

Increased evidence shows that normal stem cells may contribute to cancer development and progression by acting as cancer-initiating cells through their interactions with abnormal environmental elements. We postulate that normal stem cells and cancer stem cells (CSC) possess similar mechanisms of self-renewal and differentiation. CSC can be the key to the elaboration of anti-cancer-based therapy. In this article, we focus on a controversial new theme relating to CSC. Tumorigenesis may have a critical stage characterized as a "therapeutic window", which can be identified by association of molecular, biochemical and biological events. Identifying such a stage can allow the production of more effective therapies (e.g. manipulated stem cells) to treat several cancers. More importantly, confirming the existence of a similar therapeutic window during the conversion of normal stem cells to malignant CSC may lead to targeted therapy specifically against CSC. This conversion information may be derived from investigating the biological behaviour of both normal stem cells and cancerous stem cells. Currently, there is little knowledge about the cellular and molecular mechanisms that govern the initiation and maintenance of CSC. Studies on co-evolution and interdependence of cancer with normal tissues may lead to a useful treatment paradigm of cancer. The crosstalk between normal stem cells and cancer formation may converge developmental stages of different types of stem cells (e.g. normal stem cells, CSC and embryonic stem cells). The differential studies of the convergence may result in novel therapies for treating cancers.

摘要

越来越多的证据表明,正常干细胞可能通过与异常环境因素相互作用成为癌症起始细胞,从而促进癌症的发生和发展。我们假设正常干细胞和癌症干细胞(CSC)具有相似的自我更新和分化机制。CSC 可能是制定基于抗癌治疗的关键。本文聚焦于一个与 CSC 相关的有争议的新主题。肿瘤发生可能有一个关键阶段,其特征是“治疗窗口”,可以通过分子、生化和生物学事件的关联来识别。确定这样一个阶段可以产生更有效的治疗方法(例如,操纵干细胞)来治疗多种癌症。更重要的是,在正常干细胞向恶性 CSC 转化过程中确认存在类似的治疗窗口,可能会导致针对 CSC 的靶向治疗。这种转化信息可以通过研究正常干细胞和癌细胞的生物学行为来获得。目前,关于控制 CSC 起始和维持的细胞和分子机制知之甚少。对癌症与正常组织共同进化和相互依存的研究可能会为癌症的治疗带来有用的范例。正常干细胞和癌症形成之间的串扰可能会集中在不同类型干细胞(例如正常干细胞、CSC 和胚胎干细胞)的发育阶段。对趋同的差异研究可能会为治疗癌症带来新的疗法。

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