肿瘤是全球第二大死亡因素,也是人类关注度最高的疾病之一。 在恶性肿瘤的发生、发展过程中,肿瘤细胞通过获 得遗传和表观遗传的变异进化出一系列特征,使它们能够生存并适应肿瘤微环境(TME)的应激相关条件。 这些特征被认为 是“肿瘤的标志”,包括持续的增殖信号、肿瘤转移、血管生成、代谢重编程、抵抗细胞死亡、促肿瘤炎症等。 近年来,TME 中的 力学因素如基质硬度、流体剪切力、门静脉压力等的变化在肿瘤发生发展中的生物学作用越来越受到关注。 其中,基质硬度 也被称为细胞外基质(ECM)应力,是 TME 的一个关键物理因素。 实体肿瘤中的基质硬度由于胶原蛋白的过度产生、病理性 胶原交联和纤维排列而显著增加,而肿瘤细胞能够感知这种异常的 ECM 应力并通过其力学感受器将力学信号转化为生化信 号,加剧疾病症状。 然而,基质硬度与肿瘤发生及恶性转化的确切机制尚不完全明确。 本文综述了 ECM 力学信号在调控肿瘤 特征方面的研究进展,并讨论了靶向 ECM 硬度作为治疗肿瘤策略的可能性,为开发基于基质力学的临床肿瘤治疗提供新 思路。

Tumor is the second leading cause of death worldwide and is one of the most concerned diseases in humanity. During the occurrence and progression of malignant tumors tumor cells evolve a series of characteristics by the acquisition of genetic and epigenetic alterations that enable them to survive and adapt to stress-related conditions in the tumor microenvironment TME . These properties which are known as hallmarks of cancer include sustained proliferative signaling tumor metastasis angiogenesis metabolic reprogramming resistance to cell death and promoting tumor inflammation. Recently the biological implications of mechanical factors matrix stiffness fluid shear stress portal vein pressure etc. in TME have attracted increasing attention in tumorigenesis and development. Matrix stiffness is a key physical factor of the tumor microenvironment as known as extracellular matrix ECM stress. Studies have demonstrated that matrix stiffness in solid tumors increases significantly due to the collagen overproduction pathological collagen crosslinking and fiber alignment in turn tumor cells sense this abnormal ECM stress and convert mechanical signals into biochemical signals through their mechanical receptors and subsequently exacerbating cancer features. However the exact mechanism of matrix stiffness in tumorigenesis and malignant transformation is not fully understood. This review summarizes the study progress of ECM stiffness in regulating tumor characteristics and discusses the possibility of targeting ECM stiffness as a tumor therapeutic strategy which provides new ideas for the development of matrix mechanic-based clinical tumor therapy.