Hangzhou Normal University, Hangzhou, 311121, China.
Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, China.
Int J Biol Sci. 2024 Sep 30;20(13):5239-5253. doi: 10.7150/ijbs.102706. eCollection 2024.
Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the third leading cause of cancer deaths globally. More than 80% of HCC patients have a background of fibrosis or cirrhosis, which leads to changes in physical factors in tumor microenvironment (TME), such as increased stiffness, solid stress, fluid stresses and structural alterations in the extracellular matrix (ECM). In the past, the focus of cancer research has predominantly been on genetic and biochemical factors in the TME, and the critical role of physical factors has often been overlooked. Recent discoveries suggest these unique physical signals are converted into biochemical signals through a mechanotransduction process that influences the biological behavior of tumor cells and stromal cells. This process facilitates the occurrence and progression of tumors. This review delves into the alterations in the mechanical microenvironment during the progression of liver fibrosis to HCC, the signaling pathways activated by physical signals, and the effects on both tumor and mesenchymal stromal cells. Furthermore, this paper summarizes and discusses the therapeutic options for targeting the mechanical aspects of the TME, offering valuable insights for future research into novel therapeutic avenues against HCC and other solid tumors.
肝细胞癌（HCC）是全球第六大常见癌症，也是全球癌症死亡的第三大主要原因。超过 80%的 HCC 患者有纤维化或肝硬化的背景，这导致肿瘤微环境（TME）中的物理因素发生变化，例如增加硬度、固体应力、流体应力和细胞外基质（ECM）的结构改变。过去，癌症研究的重点主要集中在 TME 中的遗传和生化因素上，而物理因素的关键作用经常被忽视。最近的发现表明，这些独特的物理信号通过机械转导过程转化为生化信号，影响肿瘤细胞和基质细胞的生物学行为。这个过程促进了肿瘤的发生和发展。这篇综述深入探讨了肝纤维化向 HCC 进展过程中机械微环境的改变、物理信号激活的信号通路以及对肿瘤和间充质基质细胞的影响。此外，本文还总结和讨论了针对 TME 机械方面的治疗选择，为未来针对 HCC 和其他实体瘤的新型治疗途径的研究提供了有价值的见解。
