B16 Melanoma Cancer Cells with Higher Metastatic Potential are More Deformable at a Whole-Cell Level
B16 Melanoma Cancer Cells with Higher Metastatic Potential are More Deformable at a Whole-Cell Level
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DOI：
10.1007/s12195-021-00677-w
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发表时间：
2021-05-27
影响因子：
2.8
通讯作者：
Nakamura, Masanori
中科院分区：
文献类型：
--
作者：
Ujihara, Yoshihiro;Ono, Daichi;Nakamura, Masanori
转移是癌细胞从原发灶扩散到其他器官的过程。许多研究表明，当癌细胞引发转移过程时，刚度降低将有助于穿过细胞外基质。在这里，我们研究了在全细胞水平上具有不同转移潜能的黑色素瘤癌细胞的压缩特性。通过研究肌动蛋白丝结构和肌动蛋白相关基因表达，分析了它们的压缩特性差异。方法对两种转移性B16黑色素瘤变异体（B16-F1和B16-F10）进行压缩实验，以表征肿瘤细胞的整体压缩特性。进行RNA-seq分析和荧光显微成像以阐明肌动蛋白丝对整体压缩性质的贡献。结果RNA-seq分析和荧光显微成像显示B16-F10细胞中肌动蛋白丝结构不发达。B16-F10细胞的杨氏模量显著低于B16-F1细胞。在B16-F1细胞中的肌动蛋白丝的破坏使杨氏模量降低到与B16-F10细胞相同的水平，而在B16-F10细胞中的杨氏模量保持不变，无论破坏如何。结论在B16黑色素瘤细胞系中，具有高转移潜能的细胞在全细胞水平上更易变形，即使在高度变形时，肌动蛋白丝结构也不发达。这些结果意味着侵袭性癌细胞可能获得抑制肌动蛋白丝发育的能力。
Introduction Metastasis is a process in which cancer cells spread from the primary focus site to various other organ sites. Many studies have suggested that reduced stiffness would facilitate passing through extracellular matrix when cancer cells instigate a metastatic process. Here we investigated the compressive properties of melanoma cancer cells with different metastatic potentials at the whole-cell level. Differences in their compressive properties were analyzed by examining actin filament structure and actin-related gene expression. Methods Compressive tests were carried out for two metastatic B16 melanoma variants (B16-F1 and B16-F10) to characterize global compressive properties of cancer cells. RNA-seq analysis and fluorescence microscopic imaging were performed to clarify contribution of actin filaments to the global compressive properties. Results RNA-seq analysis and fluorescence microscopic imaging revealed the undeveloped structure of actin filaments in B16-F10 cells. The Young's modulus of B16-F10 cells was significantly lower than that of B16-F1 cells. Disruption of the actin filaments in B16-F1 cells reduced the Young's modulus to the same level as that of B16-F10 cells, while the Young's modulus in B16-F10 cells remained the same regardless of the disruption. Conclusions In B16 melanoma cancer cell lines, cells with higher metastatic potential were more deformable at the whole-cell level with undeveloped actin filament structure, even when highly deformed. These results imply that invasive cancer cells may gain the ability to inhibit actin filament development.