Mechanical Modulation of Ovarian Cancer Tumor Nodules Under Flow.
Mechanical Modulation of Ovarian Cancer Tumor Nodules Under Flow.
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DOI：
10.1109/tbme.2021.3092641
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Scarcelli G
中科院分区：
文献类型：
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作者：
Conrad C;Moore K;Polacheck W;Rizvi I;Scarcelli G
灌注模型是模拟肿瘤微环境复杂特征和研究细胞行为的重要工具。在卵巢癌中，通过在基底膜上播种肿瘤结节并使其长期连续流动来模拟腹水的疾病病理。在这种情况下，研究机械应力在癌症进展中的作用尤为重要。众所周知，机械信号在关键的癌症过程中起着重要作用，如生存、增殖和迁移。然而，目前的技术还无法在微流控平台内探测细胞的力学特性，因为大多数微流控通道内的样品不容易获取。在这里，为了分析灌注腔内细胞的力学特性，我们使用布里渊共聚焦显微镜，这是一种不需要接触或扰动样品的全光技术。我们的研究结果表明，长期连续流动的卵巢癌结节的纵向模量明显低于静态状态下的结节。我们进一步剖析了不同的机械扰动（如剪切流，渗透压）对肿瘤结节性质的作用。总之，长期微流体培养和无创力学分析技术的独特结合为卵巢癌病理中物理力的影响提供了见解。
Perfusion models are valuable tools to mimic complex features of the tumor microenvironment and to study cell behavior. In ovarian cancer, mimicking disease pathology of ascites has been achieved by seeding tumor nodules on a basement membrane and subjecting them to long-term continuous flow. In this scenario it is particularly important to study the role of mechanical stress on cancer progression. Mechanical cues are already known to be important in key cancer processes such as survival, proliferation, and migration. However, probing cell mechanical properties within microfluidic platforms has not been achievable with current technologies since samples are not easily accessible within most microfluidic channels. Here, to analyze the mechanical properties of cells within a perfusion chamber, we use Brillouin confocal microscopy, an all-optical technique that requires no contact or perturbation to the sample. Our results indicate that ovarian cancer nodules under long-term continuous flow have a significantly lower longitudinal modulus compared to nodules maintained in a static condition. We further dissect the role of distinct mechanical perturbations (e.g. shear flow, osmolality) on tumor nodule properties. In summary, the unique combination of a long-term microfluidic culture and noninvasive mechanical analysis technique provides insights on the effects of physical forces in ovarian cancer pathology.