Graduate School of Science and Technology, Keio University, Yokohama 223-8522, Japan.
Department of Mechanical Engineering, Faculty of Science and Technology, Keio University, Yokohama 223-8522, Japan.
Int J Mol Sci. 2022 Jun 25;23(13):7091. doi: 10.3390/ijms23137091.
In this study, we proposed an in vitro tumor model to simulate the mechanical microenvironment and investigate the effect of compressive stress on the invasion process of malignant tumors. It has been pointed out that the biomechanical environment, as well as the biochemical environment, could affect the transformation of cancer cell migration, invasion, and metastasis. We hypothesized that the solid stress caused by the exclusion of surrounding tissue could transform tumor cells from noninvasive to invasive phenotypes. Colorectal cell spheroids were embedded and cultured in agarose gels of varying concentrations to simulate the earliest stages of tumor formation and invasion. The spheroids embedded in gels at higher concentrations showed peculiar growth after 72 h of culture, and the external compressive loading imposed on them caused peculiar growth even in the gels at lower concentrations. In conclusion, the mechanical microenvironment caused the transformation of tumor cell phenotypes, promoting the growth and invasion of tumor cell spheroids.
在这项研究中，我们提出了一种体外肿瘤模型来模拟机械微环境，并研究压缩应力对恶性肿瘤侵袭过程的影响。已经指出，生物力学环境以及生化环境都会影响癌细胞迁移、侵袭和转移的转化。我们假设，周围组织的排除所产生的固有力可以使肿瘤细胞从非侵袭性表型转变为侵袭性表型。将结直肠细胞球嵌入不同浓度的琼脂糖凝胶中进行培养，以模拟肿瘤形成和侵袭的早期阶段。在培养 72 小时后，嵌入高浓度凝胶中的球体会表现出特殊的生长，而施加在它们外部的压缩负载甚至在低浓度凝胶中也会导致特殊的生长。总之，机械微环境导致肿瘤细胞表型的转化，促进了肿瘤细胞球的生长和侵袭。
