机械和ECM微环境信号在肿瘤干细胞状态测定中的整合。

IF 2.3 Q4 CELL & TISSUE ENGINEERING Current Stem Cell Reports Pub Date : 2021-03-01 Epub Date: 2020-11-23 DOI:10.1007/s40778-020-00182-2
Tiina A Jokela, Mark A LaBarge
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引用次数: 8

摘要

综述目的:肿瘤干细胞(CSCs)在肿瘤进展中发挥着核心作用。越来越多的证据表明,肿瘤微环境是调节甚至将CSC状态强加于肿瘤细胞的信号来源。这篇综述探讨了微环境来源信号的整合点,这些信号被认为在肿瘤中调节CSCs。最近的研究发现:肿瘤微环境的机械特性和细胞外基质(ECM)组成直接调节CSC状态,促进CSC生长和存活,这可能解释了某些治疗耐药模式。CSCs通过整合素和其他细胞表面受体感知机械力和ECM成分,然后激活许多细胞内信号通路。相关的信令事件是动态的,并且依赖于上下文。摘要:CSCs被认为驱动癌症转移和治疗耐药性。处于CSC状态和分化程度更高的细胞似乎是可逆的,并且取决于肿瘤微环境的组成部分。肿瘤微环境施加的信号具有组合性,最终表现为多种物理和化学信号的整合。全面了解维持细胞CSC状态的肿瘤微环境施加的信号传导可能指导未来的治疗干预。
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Integration of mechanical and ECM microenvironment signals in the determination of cancer stem cell states.

Purpose of review: Cancer stem cells (CSCs) are increasingly understood to play a central role in tumor progression. Growing evidence implicates tumor microenvironments as a source of signals that regulate or even impose CSC states on tumor cells. This review explores points of integration for microenvironment-derived signals that are thought to regulate CSCs in carcinomas.

Recent findings: CSC states are directly regulated by the mechanical properties and extra cellular matrix (ECM) composition of tumor microenvironments that promote CSC growth and survival, which may explain some modes of therapeutic resistance. CSCs sense mechanical forces and ECM composition through integrins and other cell surface receptors, which then activate a number of intracellular signaling pathways. The relevant signaling events are dynamic and context-dependent.

Summary: CSCs are thought to drive cancer metastases and therapeutic resistance. Cells that are in CSC states and more differentiated states appear to be reversible and conditional upon the components of the tumor microenvironment. Signals imposed by tumor microenvironment are of a combinatorial nature, ultimately representing the integration of multiple physical and chemical signals. Comprehensive understanding of the tumor microenvironment-imposed signaling that maintains cells in CSC states may guide future therapeutic interventions.

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来源期刊
Current Stem Cell Reports
Current Stem Cell Reports Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.30
自引率
0.00%
发文量
19
期刊介绍: The goal of this journal is to publish cutting-edge reviews on subjects pertinent to all aspects of stem cell research, therapy, ethics, commercialization, and policy. We aim to provide incisive, insightful, and balanced contributions from leading experts in each relevant domain that will be of immediate interest to a wide readership of clinicians, basic scientists, and translational investigators. We accomplish this aim by appointing major authorities to serve as Section Editors in key subject areas across the discipline. Section Editors select topics to be reviewed by leading experts who emphasize recent developments and highlight important papers published over the past year on their topics, in a crisp and readable format. We also provide commentaries from well-known figures in the field, and an Editorial Board of internationally diverse members suggests topics of special interest to their country/region and ensures that topics are current and include emerging research.
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