Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37235, United States.
Department of Bioengineering, Rice University, Houston, Texas 77030, United States.
ACS Nano. 2024 Aug 27;18(34):23637-23654. doi: 10.1021/acsnano.4c08132. Epub 2024 Aug 16.
During the metastatic cascade, cancer cells travel through the bloodstream as circulating tumor cells (CTCs) to a secondary site. Clustered CTCs have greater shear stress and treatment resistance, yet their biology remains poorly understood. We therefore engineered a tunable superhydrophobic array device (SHArD). The SHArD-C was applied to culture a clinically relevant model of CTC clusters. Using our device, we cultured a model of cancer cell aggregates of various sizes with immortalized cancer cell lines. These exhibited higher E-cadherin expression and are significantly more capable of surviving high fluid shear stress-related forces compared to single cells and model clusters grown using the control method, helping to explain why clustering may provide a metastatic advantage. Additionally, the SHArD-S, when compared with the AggreWell 800 method, provides a more consistent spheroid-forming device culturing reproducible sizes of spheroids for multiple cancer cell lines. Overall, we designed, fabricated, and validated an easily tunable engineered device which grows physiologically relevant three-dimensional (3D) cancer models containing tens to thousands of cells.
在转移级联过程中,癌细胞作为循环肿瘤细胞(CTC)通过血液流到继发性部位。聚集的 CTC 具有更大的切应力和治疗抗性,但它们的生物学特性仍知之甚少。因此,我们设计了一种可调谐的超疏水阵列器件(SHArD)。SHArD-C 被应用于培养与临床相关的 CTC 聚集模型。使用我们的设备,我们培养了不同大小的癌细胞聚集体模型,这些模型使用永生化癌细胞系。与使用对照方法培养的单个细胞和模型聚集体相比,这些细胞表现出更高的 E-钙粘蛋白表达,并且能够更好地抵抗高流体切应力相关的力,这有助于解释为什么聚集可能提供转移优势。此外,与 AggreWell 800 方法相比,SHArD-S 为多种癌细胞系提供了更一致的球体形成装置,可培养具有可重复大小的球体。总的来说,我们设计、制造并验证了一种易于调节的工程设备,该设备可培养包含数十到数千个细胞的生理相关的三维(3D)癌症模型。