Juste-Lanas Yago, Guerrero Pedro Enrique, Camacho-Gómez Daniel, Hervás-Raluy Silvia, García-Aznar Jose M, Gomez-Benito María J
Department of Mechanical Engineering, University of Zaragoza, Zaragoza 50018, Spain; Department of Biochemistry and Molecular and Cellular Biology, University of Zaragoza, Zaragoza 50009, Spain.
Department of Mechanical Engineering, University of Zaragoza, Zaragoza 50018, Spain.
J Biomech Eng. 2022 Jul 1;144(7). doi: 10.1115/1.4053143.
Metastasis, a hallmark of cancer development, is also the leading reason for most cancer-related deaths. Furthermore, cancer cells are highly adaptable to micro-environments and can migrate along pre-existing channel-like tracks of anatomical structures. However, more representative three-dimensional models are required to reproduce the heterogeneity of metastatic cell migration in vivo to further understand the metastasis mechanism and develop novel therapeutic strategies against it. Here, we designed and fabricated different microfluidic-based devices that recreate confined migration and diverse environments with asymmetric hydraulic resistances. Our results show different migratory potential between metastatic and nonmetastatic cancer cells in confined environments. Moreover, although nonmetastatic cells have not been tested against barotaxis due to their low migration capacity, metastatic cells present an enhanced preference to migrate through the lowest resistance path, being sensitive to barotaxis. This device, approaching the study of metastasis capability based on confined cell migration and barotactic cell decisions, may pave the way for the implementation of such technology to determine and screen the metastatic potential of certain cancer cells.
转移是癌症发展的一个标志，也是大多数癌症相关死亡的主要原因。此外，癌细胞对微环境具有高度适应性，能够沿着解剖结构中预先存在的通道样轨迹迁移。然而，需要更具代表性的三维模型来重现体内转移细胞迁移的异质性，以进一步了解转移机制并开发针对它的新型治疗策略。在这里，我们设计并制造了不同的基于微流控的装置，这些装置能够创建具有不对称水力阻力的受限迁移和多样环境。我们的结果显示，在受限环境中，转移性和非转移性癌细胞具有不同的迁移潜力。此外，尽管非转移性细胞由于迁移能力低尚未针对趋压性进行测试，但转移性细胞表现出更强的偏好，即通过最低阻力路径迁移，对趋压性敏感。这种基于受限细胞迁移和趋压性细胞决策来研究转移能力的装置，可能为应用此类技术来确定和筛选某些癌细胞的转移潜力铺平道路。
