A three-dimensional microfluidic tumor cell migration assay to screen the effect of anti-migratory drugs and interstitial flow
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Author(s)
Kalchman, Johann
Fujioka, Shingo
Chung, Seok
Kikkawa, Yamato
Mitaka, Toshihiro
Tanishita, Kazuo
Sudo, Ryo
Kamm, Roger Dale
Date Issued
December 2012
Journal
Microfluidics and Nanofluidics
Publisher
Springer-Verlag
Citation
Kalchman, Johann, Shingo Fujioka, Seok Chung, Yamato Kikkawa, Toshihiro Mitaka, Roger D. Kamm, Kazuo Tanishita, and Ryo Sudo. “A Three-Dimensional Microfluidic Tumor Cell Migration Assay to Screen the Effect of Anti-Migratory Drugs and Interstitial Flow.” Microfluidics and Nanofluidics 14, no. 6 (December 4, 2012): 969–981.
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Author's final manuscript
Abstract
Most anti-cancer drug screening assays are currently performed in two dimensions, on flat, rigid surfaces. However, there are increasing indications that three-dimensional (3D) platforms provide a more realistic setting to investigate accurate morphology, growth, and sensitivity of tumor cells to chemical factors. Moreover, interstitial flow plays a pivotal role in tumor growth. Here, we present a microfluidic 3D platform to investigate behaviors of tumor cells in flow conditions with anti-migratory compounds. Our results show that interstitial flow and its direction have significant impact on migration and growth of hepatocellular carcinoma cell lines such as HepG2 and HLE. In particular, HepG2/HLE cells tend to migrate against interstitial flow, and their growth increases in interstitial flow conditions regardless of the flow direction. Furthermore, this migratory activity of HepG2 cells is enhanced when they are co-cultured with human umbilical vein endothelial cells. We also found that migration activity of HepG2 cells attenuates under hypoxic conditions. In addition, the effect of Artemisinin, an anti-migratory compound, on HepG2 cells was quantitatively analyzed. The microfluidic 3D platform described here is useful to investigate more accurately the effect of anti-migratory drugs on tumor cells and the critical influence of interstitial flow than 2D culture models.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
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DOI of Published Version
https://doi.org/10.1007/s10404-012-1104-6
