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基质硬度影响肿瘤相关巨噬细胞功能极化及其在肿瘤治疗中的潜力。

Matrix stiffness affects tumor-associated macrophage functional polarization and its potential in tumor therapy.

机构信息

Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.

Department of Medical Genetics, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China.

出版信息

J Transl Med. 2024 Jan 21;22(1):85. doi: 10.1186/s12967-023-04810-3.

DOI:10.1186/s12967-023-04810-3
PMID:38246995
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10800063/
Abstract

The extracellular matrix (ECM) plays critical roles in cytoskeletal support, biomechanical transduction and biochemical signal transformation. Tumor-associated macrophage (TAM) function is regulated by matrix stiffness in solid tumors and is often associated with poor prognosis. ECM stiffness-induced mechanical cues can activate cell membrane mechanoreceptors and corresponding mechanotransducers in the cytoplasm, modulating the phenotype of TAMs. Currently, tuning TAM polarization through matrix stiffness-induced mechanical stimulation has received increasing attention, whereas its effect on TAM fate has rarely been summarized. A better understanding of the relationship between matrix stiffness and macrophage function will contribute to the development of new strategies for cancer therapy. In this review, we first introduced the overall relationship between macrophage polarization and matrix stiffness, analyzed the changes in mechanoreceptors and mechanotransducers mediated by matrix stiffness on macrophage function and tumor progression, and finally summarized the effects of targeting ECM stiffness on tumor prognosis to provide insight into this new field.

摘要

细胞外基质 (ECM) 在细胞骨架支持、生物力学转导和生化信号转化中起着关键作用。肿瘤相关巨噬细胞 (TAM) 的功能受实体瘤中基质硬度的调节，通常与预后不良有关。ECM 硬度诱导的机械线索可以激活细胞膜机械感受器和细胞质中的相应机械转导器，调节 TAM 的表型。目前，通过基质硬度诱导的机械刺激来调节 TAM 极化受到越来越多的关注，而其对 TAM 命运的影响很少被总结。更好地了解基质硬度与巨噬细胞功能之间的关系将有助于开发癌症治疗的新策略。在这篇综述中，我们首先介绍了巨噬细胞极化和基质硬度之间的总体关系，分析了基质硬度介导的机械感受器和机械转导器对巨噬细胞功能和肿瘤进展的变化，最后总结了靶向 ECM 硬度对肿瘤预后的影响，为这一新领域提供了深入了解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53f9/10800063/ad3cc4de417d/12967_2023_4810_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53f9/10800063/3a759bf24e6e/12967_2023_4810_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53f9/10800063/544cd151b452/12967_2023_4810_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53f9/10800063/2bf916ff7978/12967_2023_4810_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53f9/10800063/ad3cc4de417d/12967_2023_4810_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53f9/10800063/3a759bf24e6e/12967_2023_4810_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53f9/10800063/544cd151b452/12967_2023_4810_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53f9/10800063/2bf916ff7978/12967_2023_4810_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53f9/10800063/ad3cc4de417d/12967_2023_4810_Fig4_HTML.jpg

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