Department of Oncological Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
Department of Neurobiology, Harbin Medical University, Harbin, 150081, China.
Mol Cancer. 2023 Mar 11;22(1):48. doi: 10.1186/s12943-023-01744-8.
The malignant tumor is a multi-etiological, systemic and complex disease characterized by uncontrolled cell proliferation and distant metastasis. Anticancer treatments including adjuvant therapies and targeted therapies are effective in eliminating cancer cells but in a limited number of patients. Increasing evidence suggests that the extracellular matrix (ECM) plays an important role in tumor development through changes in macromolecule components, degradation enzymes and stiffness. These variations are under the control of cellular components in tumor tissue via the aberrant activation of signaling pathways, the interaction of the ECM components to multiple surface receptors, and mechanical impact. Additionally, the ECM shaped by cancer regulates immune cells which results in an immune suppressive microenvironment and hinders the efficacy of immunotherapies. Thus, the ECM acts as a barrier to protect cancer from treatments and supports tumor progression. Nevertheless, the profound regulatory network of the ECM remodeling hampers the design of individualized antitumor treatment. Here, we elaborate on the composition of the malignant ECM, and discuss the specific mechanisms of the ECM remodeling. Precisely, we highlight the impact of the ECM remodeling on tumor development, including proliferation, anoikis, metastasis, angiogenesis, lymphangiogenesis, and immune escape. Finally, we emphasize ECM "normalization" as a potential strategy for anti-malignant treatment.
恶性肿瘤是一种多病因、系统性和复杂性疾病，其特征是细胞不受控制地增殖和远处转移。包括辅助治疗和靶向治疗在内的抗癌治疗方法在消除癌细胞方面非常有效，但只对少数患者有效。越来越多的证据表明，细胞外基质（ECM）通过改变大分子成分、降解酶和硬度，在肿瘤发展中起着重要作用。这些变化受肿瘤组织中细胞成分的控制，通过信号通路的异常激活、ECM 成分与多个表面受体的相互作用以及机械影响。此外，由癌细胞形成的 ECM 调节免疫细胞，导致免疫抑制微环境，从而阻碍免疫疗法的疗效。因此，ECM 作为一种保护癌症免受治疗的屏障，支持肿瘤的进展。然而，ECM 重塑的深刻调控网络阻碍了个体化抗肿瘤治疗的设计。在这里，我们详细阐述了恶性 ECM 的组成，并讨论了 ECM 重塑的具体机制。具体来说，我们强调了 ECM 重塑对肿瘤发展的影响，包括增殖、失巢凋亡、转移、血管生成、淋巴管生成和免疫逃逸。最后，我们强调 ECM“正常化”作为一种潜在的抗恶性治疗策略。
