Nano-scale physical properties characteristic to intestinal cancer cells identified by high speed-scanning ion conductance microscope
Nano-scale physical properties characteristic to intestinal cancer cells identified by high speed-scanning ion conductance microscope
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高速扫描离子电导显微镜鉴定肠癌细胞的纳米级物理特性
DOI：
10.1016/j.biomaterials.2021.121256
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发表时间：
2022
期刊：
影响因子：
14
通讯作者：
M. Oshima
中科院分区：
文献类型：
--
作者：
D. Wang;L. Sun;S. Okuda;D. Yamamoto;M. Nakayama;H. Oshima;H. Saito;Y. Kouyama;K. Mimori;T. Ando;S. Watanabe;M. Oshima
最近的遗传学研究表明，基因突变与结肠癌表型之间存在关系。然而，肿瘤细胞的物理性质是如何通过基因改变而改变的，目前还没有得到阐明。我们使用高速扫描离子电导显微镜（HS-SICM）检测基因型定义的小鼠肠道肿瘤来源细胞，该显微镜可以获得纳米级形貌和硬度的高分辨率实时图像。本研究中使用的肿瘤细胞携带apc (A)、Kras(K)、Tgfbr2(T)、Trp53(P)和fbxw7 (F)以不同的组合突变。值得注意的是，携带AKT突变（AKT、AKTP和AKTPF）的高转移性癌源性细胞表现出特定的脊状形态和活跃的膜体积变化，而这在低转移性和腺瘤源性细胞中没有发现。此外，与其他基因型细胞相比，转移性akt型癌细胞的细胞膜明显变软。重要的是，使用RNAseq数据的主成分分析显示了相似的表达谱分布和物理特性，表明遗传改变和物理特性之间存在联系。最后，利用人结肠癌源性细胞，通过HS-SICM证实了恶性细胞特异性物理特性。这些结果表明，HS-SICM分析可作为预测癌细胞转移能力的一种新的诊断策略。
Recent genetic studies have indicated relationships between gene mutations and colon cancer phenotypes. However, how physical properties of tumor cells are changed by genetic alterations has not been elucidated. We examined genotype-defined mouse intestinal tumor-derived cells using a high-speed scanning ion conductance microscope (HS-SICM) that can obtain high-resolution live images of nano-scale topography and stiffness. The tumor cells used in this study carried mutations inApc(A),Kras(K),Tgfbr2(T),Trp53(P), andFbxw7(F) in various combinations. Notably, high-metastatic cancer-derived cells carrying AKT mutations (AKT, AKTP, and AKTPF) showed specific ridge-like morphology with active membrane volume change, which was not found in low-metastatic and adenoma-derived cells. Furthermore, the membrane was significantly softer in the metastatic AKT-type cancer cells than other genotype cells. Importantly, a principal component analysis using RNAseq data showed similar distributions of expression profiles and physical properties, indicating a link between genetic alterations and physical properties. Finally, the malignant cell-specific physical properties were confirmed by an HS-SICM using human colon cancer-derived cells. These results indicate that the HS-SICM analysis is useful as a novel diagnostic strategy for predicting the metastatic ability of cancer cells.