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用于增强 3D 癌症模型形成的超疏水阵列器件。

Superhydrophobic Array Devices for the Enhanced Formation of 3D Cancer Models.

机构信息

Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37235, United States.

Department of Bioengineering, Rice University, Houston, Texas 77030, United States.

出版信息

ACS Nano. 2024 Aug 27;18(34):23637-23654. doi: 10.1021/acsnano.4c08132. Epub 2024 Aug 16.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6711/11363216/a68f747a99b1/nn4c08132_0001.jpg

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