Key Laboratory of Biorheological Science and Technology, College of Bioengineering, Chongqing University, Ministry of Education, Chongqing, 400030, People's Republic of China.
Histochem Cell Biol. 2021 Jul;156(1):47-58. doi: 10.1007/s00418-021-01979-w. Epub 2021 Mar 12.
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局限于特定的肿瘤微环境，而这个微环境在肿瘤的发展中起着至关重要的作用。微环境的力学特性在固体肿瘤的不同区域有所不同。然而，在实体肿瘤中，癌症干细胞的分布是否与不同区域的力学微环境有关尚不清楚。在这项研究中，我们对肝癌发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，并探讨了肝癌组织中肝癌干细胞的分布。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逐渐增加。在肝癌组织中，我们发现了明显的力学异质性：肿瘤的核心部位较软，侵袭前沿组织硬度最高，癌旁组织处于中间状态。有趣的是，在肿瘤侵袭前沿部分发现了最多数量的肝癌干细胞。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力学异质性相关。这一结果为针对肝癌干细胞力学微环境的靶向治疗提供了理论依据。
