The survival of cancer stem cells is usually limited to a specific tumor microenvironment, and this microenvironment plays a vital role in the development of tumors. The mechanical properties of the microenvironment differ in different regions of solid tumors. However, in solid tumors, whether the distribution of cancer stem cells relates to the mechanical microenvironment of different regions is still unclear. In this study, we undertook a biophysical and biochemical assessment of the changes in the mechanical properties of liver tissue during the progression of liver cancer and explored the distribution of liver cancer stem cells in liver cancer tissues. Our analysis confirmed previous observations that the stiffness of liver tissue gradually increased with the progress of fibrosis. In liver cancer tissues, we found obvious mechanical heterogeneity: the core of the tumor was soft, the invasive front tissue was the hardest, and the para-cancer tissue was in an intermediate state. Interestingly, the greatest number of liver cancer stem cells was found in the invasive front part of the tumor. We finally established that stroma stiffness correlated with the number of liver cancer stem cells. These findings indicate that the distribution of liver cancer stem cells correlates with the mechanical heterogeneity of liver cancer tissue. This result provides a theoretical basis for the development of targeted therapies against the mechanical microenvironment of liver cancer stem cells.

癌症干细胞的存活通常仅限于特定的肿瘤微环境，而这种微环境在肿瘤的发展中起着至关重要的作用。微环境的机械特性在实体瘤的不同区域有所不同。然而，在实体瘤中，肿瘤干细胞的分布是否与不同区域的机械微环境有关尚不清楚。本研究对肝癌进展过程中肝组织力学特性的变化进行了生物物理和生化评估，并探讨了肝癌干细胞在肝癌组织中的分布。我们的分析证实了先前的观察结果，即肝组织的硬度随着纤维化的进展而逐渐增加。在肝癌组织中，我们发现明显的机械异质性：肿瘤核心较软，浸润前沿组织最硬，癌旁组织处于中间状态。有趣的是，在肿瘤的侵袭性前部发现了数量最多的肝癌干细胞。我们最终确定基质硬度与肝癌干细胞的数量相关。这些发现表明肝癌干细胞的分布与肝癌组织的机械异质性相关。该结果为开发针对肝癌干细胞机械微环境的靶向治疗提供了理论依据。在肿瘤的侵袭性前部发现了数量最多的肝癌干细胞。我们最终确定基质硬度与肝癌干细胞的数量相关。这些发现表明肝癌干细胞的分布与肝癌组织的机械异质性相关。该结果为开发针对肝癌干细胞机械微环境的靶向治疗提供了理论依据。在肿瘤的侵袭性前部发现了数量最多的肝癌干细胞。我们最终确定基质硬度与肝癌干细胞的数量相关。这些发现表明肝癌干细胞的分布与肝癌组织的机械异质性相关。该结果为开发针对肝癌干细胞机械微环境的靶向治疗提供了理论依据。