Natural Product Informatics Research Center, Korea Institute of Science and Technology (KIST), Gangwon-do 25451, Gangneung-si, South Korea.
Department of Pharmacy, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Korea.
Arch Pharm Res. 2020 Nov;43(11):1162-1172. doi: 10.1007/s12272-020-01291-6. Epub 2020 Nov 21.
Cancer metastasis involves diverse cellular functions via bidirectional communications between intracellular and extracellular spaces. To achieve development of the anti-metastatic drugs, one needs to consider the efficacy and mode of action (MOA) of the drug candidates to block the metastatic potentials of cancerous cells. Rather than under two-dimensional environment, investigation of the metastatic potentials under three-dimensional environment would be much pharmaceutically beneficent, since it can mimic the in vivo tumor lesions in cancer patients, leading to allowance of drug candidates analyzed in the 3D culture systems to lower failure rates during the anti-metastatic drug development. Here we have reviewed on the analyses of metastatic potentials of certain cancer models in 3D culture systems surrounded with extracellular matrix proteins, which could be supported by TM4SF5- and/or EMT-mediated actions. We particularly focused the initial events of the cancer metastasis, such as invasive outgrowth and dissemination from the cancer cell masses, spheroids, embedded in the 3D gel culture systems. This review summarizes the significance of tetraspanin TM4SF5 and Snail1 that are related to EMT in the metastatic potentials explored in the 3D gel systems.
癌症转移涉及细胞内和细胞外空间之间的双向通讯，通过多种细胞功能来实现。为了开发抗转移药物，需要考虑药物候选物的疗效和作用模式 (MOA)，以阻断癌细胞的转移潜力。在三维环境下研究转移潜力比在二维环境下更有利于药物开发，因为它可以模拟癌症患者体内的肿瘤病变，从而降低抗转移药物开发过程中药物候选物分析的失败率。在这里，我们综述了在细胞外基质蛋白包围的三维培养系统中某些癌症模型转移潜力的分析，这些分析可以通过 TM4SF5 和/或 EMT 介导的作用来支持。我们特别关注癌症转移的初始事件，例如从癌细胞团块、球体中侵入性生长和扩散，这些球体嵌入在三维凝胶培养系统中。这篇综述总结了与 EMT 相关的四跨膜蛋白 TM4SF5 和 Snail1 在三维凝胶系统中探索的转移潜力中的意义。
