Zhang Meiling, Zhang Bin
School of Basic Medicine, China Three Gorges University, 8 Daxue Road, Yichang, 443002, Hubei, China.
Central Laboratory, The First Affiliated Hospital of Jinan University, No. 613 Huangpu West Road, Tianhe District, Guangzhou, 510627, Guangdong, China.
Exp Hematol Oncol. 2025 Apr 10;14(1):54. doi: 10.1186/s40164-025-00647-2.
Tumor microenvironment (TME) is a complex ecosystem composed of both cellular and non-cellular components that surround tumor tissue. The extracellular matrix (ECM) is a key component of the TME, performing multiple essential functions by providing mechanical support, shaping the TME, regulating metabolism and signaling, and modulating immune responses, all of which profoundly influence cell behavior. The quantity and cross-linking status of stromal components are primary determinants of tissue stiffness. During tumor development, ECM stiffness not only serves as a barrier to hinder drug delivery but also promotes cancer progression by inducing mechanical stimulation that activates cell membrane receptors and mechanical sensors. Thus, a comprehensive understanding of how ECM stiffness regulates tumor progression is crucial for identifying potential therapeutic targets for cancer. This review examines the effects of ECM stiffness on tumor progression, encompassing proliferation, migration, metastasis, drug resistance, angiogenesis, epithelial-mesenchymal transition (EMT), immune evasion, stemness, metabolic reprogramming, and genomic stability. Finally, we explore therapeutic strategies that target ECM stiffness and their implications for tumor progression.
肿瘤微环境（TME）是一个由围绕肿瘤组织的细胞和非细胞成分组成的复杂生态系统。细胞外基质（ECM）是TME的关键组成部分，通过提供机械支持、塑造TME、调节代谢和信号传导以及调节免疫反应来执行多种重要功能，所有这些都会深刻影响细胞行为。基质成分的数量和交联状态是组织硬度的主要决定因素。在肿瘤发展过程中，ECM硬度不仅作为阻碍药物递送的屏障，还通过诱导激活细胞膜受体和机械传感器的机械刺激来促进癌症进展。因此，全面了解ECM硬度如何调节肿瘤进展对于确定癌症的潜在治疗靶点至关重要。本综述探讨了ECM硬度对肿瘤进展的影响，包括增殖、迁移、转移、耐药性、血管生成、上皮-间质转化（EMT）、免疫逃逸、干性、代谢重编程和基因组稳定性。最后，我们探索了针对ECM硬度的治疗策略及其对肿瘤进展的影响。
