The tumor microenvironment (TME) is critical for cancer initiation, growth, metastasis, and therapeutic resistance. The extracellular matrix (ECM) is a significant tumor component that serves various functions, including mechanical support, TME regulation, and signal molecule generation. The quantity and cross‐linking status of ECM components are crucial factors in tumor development, as they determine tissue stiffness and the interaction between stiff TME and cancer cells, resulting in aberrant mechanotransduction, proliferation, migration, invasion, angiogenesis, immune evasion, and treatment resistance. Therefore, broad knowledge of ECM dysregulation in the TME might aid in developing innovative cancer therapies. This review summarized the available information on major ECM components, their functions, factors that increase and decrease matrix stiffness, and related signaling pathways that interplay between cancer cells and the ECM in TME. Moreover, mechanotransduction alters during tumorogenesis, and current drug therapy based on ECM as targets, as well as future efforts in ECM and cancer, are also discussed.

中文翻译：

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深入了解癌症细胞外基质硬度的机制、调节和治疗意义


肿瘤微环境（TME）对于癌症的发生、生长、转移和治疗耐药至关重要。细胞外基质 (ECM) 是重要的肿瘤成分，具有多种功能，包括机械支持、TME 调节和信号分子生成。 ECM成分的数量和交联状态是肿瘤发展的关键因素，因为它们决定组织硬度以及僵硬的TME和癌细胞之间的相互作用，从而导致异常的机械转导、增殖、迁移、侵袭、血管生成、免疫逃避和治疗反抗。因此，对 TME 中 ECM 失调的广泛了解可能有助于开发创新的癌症疗法。本综述总结了关于主要 ECM 成分、其功能、增加和减少基质硬度的因素以及 TME 中癌细胞与 ECM 之间相互作用的相关信号通路的可用信息。此外，还讨论了肿瘤发生过程中机械转导的变化、当前以 ECM 为靶点的药物治疗以及未来在 ECM 和癌症方面的努力。