Mechanical Properties of Colorectal Cancer Cells Determined by Dynamic Atomic Force Microscopy: A Novel Biomarker.

Mechanical Properties of Colorectal Cancer Cells Determined by Dynamic Atomic Force Microscopy: A Novel Biomarker.
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DOI:
10.3390/cancers14205053
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发表时间:
2022-10-15
期刊:
影响因子:
5.2
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
作者:

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结直肠癌(CRC)是目前世界上第三大和第二大致死性癌症。因此,有一个真实的和迫切的需要,以调查背后的CRC细胞的出现,发展和增殖的过程。已经研究了几种生化途径以了解它们在癌基因激活和肿瘤抑制基因抑制中的作用。尽管生物化学的研究有所增加,但仍然需要更好地了解驱动与机械转导和细胞转化相关的信号转导途径激活的生物物理线索。这些生物学过程的阐明可能有助于阻碍致癌机制,并找到可用于设计更个性化的治疗策略的生物标志物。结直肠癌(CRC)已经在分子、细胞生物学和生物化学特征的框架内得到解决。研究CRC的一种新方法是关注生化途径和生物物理线索之间的关系,这可能有助于疾病的理解和治疗的发展。在此,我们研究了CRC细胞,即,HCT 116,HCT 15,和SW 620的机械性能,使用静态和动态的方法,通过原子力显微镜(AFM)。静态方法量化杨氏模量;动态方法允许测定弹性、粘度和流动性。原子力显微镜的结果与共聚焦激光扫描显微镜和细胞迁移试验数据。SW 620转移性细胞呈现最高的杨氏模量和储能模量,具有定义的皮质肌动蛋白环和分布的F-肌动蛋白丝,缺乏黏着斑蛋白表达,丰富的总粘着斑(FAK),并且没有丝状伪足形成,这可以解释迁移行为的减少。相比之下,HCT 15细胞呈现较低的杨氏模量和储能模量,高皮质微管蛋白,较少的皮质F-肌动蛋白和较少的FAK,以及更多的丝状伪足形成,这可能解释了较高的迁移行为。HCT 116细胞呈现出介于其他细胞系之间的杨氏模量和储能模量值,高皮质F-肌动蛋白表达,中等水平的总FAK和丰富的丝状伪足形成,这可能解释了最高的迁移行为。
Colorectal cancer (CRC) is presently the third-most abundant and the second-most lethal cancer worldwide. Thus, there is a real and urgent need to investigate the processes behind the appearance, development, and proliferation of CRC cells. Several biochemical pathways have been investigated to understand their role in oncogene activation and tumor-suppressor gene inhibition. Despite the research increase in biochemistry, there is still a need to better understand the biophysical cues that drive the activation of signaling pathways relevant to mechanotransduction and cell transformation. The elucidation of these biological processes may help to hinder oncogenic mechanisms and to find biomarkers that could be used to design more personalized therapeutic strategies. Colorectal cancer (CRC) has been addressed in the framework of molecular, cellular biology, and biochemical traits. A new approach to studying CRC is focused on the relationship between biochemical pathways and biophysical cues, which may contribute to disease understanding and therapy development. Herein, we investigated the mechanical properties of CRC cells, namely, HCT116, HCT15, and SW620, using static and dynamic methodologies by atomic force microscopy (AFM). The static method quantifies Young’s modulus; the dynamic method allows the determination of elasticity, viscosity, and fluidity. AFM results were correlated with confocal laser scanning microscopy and cell migration assay data. The SW620 metastatic cells presented the highest Young’s and storage moduli, with a defined cortical actin ring with distributed F-actin filaments, scarce vinculin expression, abundant total focal adhesions (FAK), and no filopodia formation, which could explain the lessened migratory behavior. In contrast, HCT15 cells presented lower Young’s and storage moduli, high cortical tubulin, less cortical F-actin and less FAK, and more filopodia formation, probably explaining the higher migratory behavior. HCT116 cells presented Young’s and storage moduli values in between the other cell lines, high cortical F-actin expression, intermediate levels of total FAK, and abundant filopodia formation, possibly explaining the highest migratory behavior.
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发表时间: 2022-05-23
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影响因子: 5
作者:
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