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肿瘤相关间充质干细胞:新兴的治疗靶点。

Tumour-associated mesenchymal stem/stromal cells: emerging therapeutic targets.

机构信息

The First Affiliated Hospital of Soochow University and Jiangsu Engineering Research Center for Tumor Immunotherapy, Institutes for Translational Medicine and Suzhou Key Laboratory of Tumor Microenvironment and Pathology, Soochow University, 199 Renai Road, Suzhou, Jiangsu 215123, China.

Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901, USA.

出版信息

Nat Rev Drug Discov. 2017 Jan;16(1):35-52. doi: 10.1038/nrd.2016.193. Epub 2016 Nov 4.


DOI:10.1038/nrd.2016.193
PMID:27811929
Abstract

Mesenchymal stem cells, also known as mesenchymal stromal cells (MSCs), exist in many tissues and are known to actively migrate to sites of tissue injury, where they participate in wound repair. Tumours can be considered "wounds that never heal" and, in response to cues from a tumour, MSCs are continuously recruited to and become integral components of the tumour microenvironment. Recently, it has become apparent that such tumour-associated MSCs (TA-MSCs) have an active role in tumour initiation, promotion, progression and metastasis. In this Review, we discuss recent advances in our understanding of the pathogenic role of TA-MSCs in regulating the survival, proliferation, migration and drug resistance of tumour cells, as well as the influence of MSCs on the immune status of the tumour microenvironment. Moreover, we discuss therapeutic approaches that target TA-MSC upstream or downstream modulators or use MSCs as vehicles for the delivery of tumoricidal agents. It is anticipated that new insights into the functions of TA-MSCs will lead to the development of novel therapeutic strategies against tumours.

摘要

间充质干细胞,也称为间充质基质细胞(MSCs),存在于许多组织中,已知它们会主动迁移到组织损伤部位,参与伤口修复。肿瘤可以被认为是“永不愈合的伤口”,并且,对肿瘤发出的信号做出反应,间充质干细胞不断被招募并成为肿瘤微环境的组成部分。最近,人们已经清楚地认识到,这种与肿瘤相关的间充质干细胞(TA-MSCs)在肿瘤的起始、促进、进展和转移中具有积极作用。在这篇综述中,我们讨论了对 TA-MSCs 在调节肿瘤细胞的存活、增殖、迁移和耐药性方面的致病作用的最新认识,以及间充质干细胞对肿瘤微环境免疫状态的影响。此外,我们还讨论了针对 TA-MSC 上游或下游调节剂的治疗方法,或使用间充质干细胞作为递送肿瘤杀伤剂的载体。预计对 TA-MSCs 功能的新见解将导致开发针对肿瘤的新治疗策略。

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本文引用的文献

[1]
TNFα-activated mesenchymal stromal cells promote breast cancer metastasis by recruiting CXCR2 neutrophils.

Oncogene. 2017-1-26

[2]
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Oncogene. 2016-11-17

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Cell. 2016-2-25

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Suicide Gene-Engineered Stromal Cells Reveal a Dynamic Regulation of Cancer Metastasis.

Sci Rep. 2016-2-19

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Application of Mesenchymal Stem Cells in Melanoma: A Potential Therapeutic Strategy for Delivery of Targeted Agents.

Curr Med Chem. 2016

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Neutrophils support lung colonization of metastasis-initiating breast cancer cells.

Nature. 2015-12-17

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Int Immunol. 2015-10

[8]
Bone marrow mesenchymal stem cells suppress metastatic tumor development in mouse by modulating immune system.

Stem Cell Res Ther. 2015-3-24

[9]
Treatment of advanced gastrointestinal tumors with genetically modified autologous mesenchymal stromal cells (TREAT-ME1): study protocol of a phase I/II clinical trial.

BMC Cancer. 2015-4-8

[10]
Stromal contribution to the colorectal cancer transcriptome.

Nat Genet. 2015-2-23

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