We have developed a bladder cancer-on-a-chip model which supports the 3D growth of cells and can be used to assess and quantify bladder cancer cell invasiveness in a physiologically appropriate environment. Three bladder cancer cell lines (T24, J82, and RT4) were resuspended in 50% Matrigel®and grown within a multi-channel organ-on-a-chip system. The ability of live cells to invade across into an adjacent 50% Matrigel®-only channel was assessed over a 2-day period. Cell lines isolated from patients with high-grade bladder cancer (T24 and J82) invaded across into the Matrigel®-only channel at a much higher frequency compared to cells isolated from a patient with low-grade cancer (RT4) (p< 0.001). The T24 and J82 cells also invaded further distances into the Matrigel®-only channel compared to the RT4 cells (p< 0.001). The cell phenotype within the model was maintained as assessed by cell morphology and immunohistochemical analysis of E-cadherin. Treatment with ATN-161, an α5β1 integrin inhibitor and well-known migrastatic drug, caused a dose-dependent decrease in the invasiveness of the J82 cells (p< 0.01). The combined data demonstrate that our bladder cancer-on-a-chip model supports the retention of the bladder cancer cell phenotype and can be used to reproducibly assess and quantify the invasiveness of live bladder cancer cells.
我们开发了一种膀胱癌芯片模型，该模型支持细胞的三维生长，并能在生理适宜环境中评估和量化膀胱癌细胞的侵袭能力。将三种膀胱癌细胞系（T24、J82和RT4）重悬于50%基质胶中，并在多通道器官芯片系统内培养。通过为期两天的观察，评估活细胞向相邻纯50%基质胶通道的侵袭能力。与低级别膀胱癌患者来源的细胞（RT4）相比，高级别膀胱癌患者来源的细胞系（T24和J82）向纯基质胶通道的侵袭频率显著更高（p<0.001）。相较于RT4细胞，T24和J82细胞在纯基质胶通道中的侵袭距离也更远（p<0.001）。通过细胞形态学观察和E-钙黏蛋白免疫组化分析证实，该模型中的细胞表型得以维持。使用α5β1整合素抑制剂ATN-161（一种公认的迁移抑制药物）处理J82细胞后，其侵袭能力呈现剂量依赖性下降（p<0.01）。综合数据表明，我们的膀胱癌芯片模型能够维持膀胱癌细胞表型特征，并可用于可重复地评估和量化活体膀胱癌细胞的侵袭能力。
Development of a Bladder Cancer-on-a-Chip Model to Assess Bladder Cancer Cell Invasiveness
肿瘤(癌症)患者之家