用于快速量化转移潜力的高通量微加工平台。
A high-throughput microfabricated platform for rapid quantification of metastatic potential.
发表日期:2024 Aug 16
作者:
Smiti Bhattacharya, Abora Ettela, Jonathan Haydak, Chad M Hobson, Alan Stern, Miran Yoo, Teng-Leong Chew, G Luca Gusella, Emily J Gallagher, James C Hone, Evren U Azeloglu
来源:
DIABETES & METABOLISM
摘要:
测量形态、增殖、运动、变形性和迁移的测定用于研究癌细胞的侵袭性。然而,细胞的天然侵袭潜力可能隐藏在这些背景指标中,因为它们取决于培养条件。我们创建了一种微图案芯片,可以模仿天然环境条件,量化肿瘤细胞的侵袭潜力,并提高我们对恶性肿瘤特征的理解。与依赖于转移潜力的间接测量的传统测定不同,我们的方法使用三维微通道来测量基础天然侵袭性,而无需化学引诱剂或微流体。在我们的芯片上没有观察到细胞死亡或增殖的变化。使用六种癌细胞系,我们表明我们的系统比其他基于运动的测定、核变形性测量或细胞形态测量更敏感。除了量化转移潜力之外,我们的平台还可以区分运动性和侵袭性,帮助研究侵袭的分子机制,并筛选靶向治疗方法。
Assays that measure morphology, proliferation, motility, deformability, and migration are used to study the invasiveness of cancer cells. However, native invasive potential of cells may be hidden from these contextual metrics because they depend on culture conditions. We created a micropatterned chip that mimics the native environmental conditions, quantifies the invasive potential of tumor cells, and improves our understanding of the malignancy signatures. Unlike conventional assays, which rely on indirect measurements of metastatic potential, our method uses three-dimensional microchannels to measure the basal native invasiveness without chemoattractants or microfluidics. No change in cell death or proliferation is observed on our chips. Using six cancer cell lines, we show that our system is more sensitive than other motility-based assays, measures of nuclear deformability, or cell morphometrics. In addition to quantifying metastatic potential, our platform can distinguish between motility and invasiveness, help study molecular mechanisms of invasion, and screen for targeted therapeutics.