Barbara T. Murphy Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Mechanical Engineering, Columbia University, New York, NY, USA.
Sci Adv. 2024 Aug 16;10(33):eadk0015. doi: 10.1126/sciadv.adk0015.
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.
用于研究癌细胞侵袭性的检测方法有形态学、增殖、运动性、变形性和迁移性检测等。然而，由于这些检测方法依赖于培养条件，细胞的固有侵袭潜能可能会被这些环境因素所掩盖。我们创建了一种微图案芯片，可以模拟自然环境条件，定量评估肿瘤细胞的侵袭潜能，从而增进我们对恶性特征的理解。与传统的依赖于转移潜能间接测量的检测方法不同，我们的方法使用三维微通道在没有趋化因子或微流控的情况下测量基底固有侵袭性。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性的检测方法、核变形性的测量或细胞形态计量学更灵敏。除了定量评估转移潜能外，我们的平台还可以区分运动性和侵袭性，有助于研究侵袭的分子机制，并筛选靶向治疗药物。
