A three-dimensional microfluidic tumor cell migration assay to screen the effect of anti-migratory drugs and interstitial flow

Johann Kalchman, Shingo Fujioka, Seok Chung, Yamato Kikkawa, Toshihiro Mitaka, Roger D. Kamm, Kazuo Tanishita, Ryo Sudo*

*この研究の対応する著者

研究成果: Article査読

26 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)969-981
ページ数13
ジャーナルMicrofluidics and Nanofluidics
14
6
DOI
出版ステータスPublished - 2013 6月
外部発表はい

ASJC Scopus subject areas

  • 凝縮系物理学
  • 電子材料、光学材料、および磁性材料
  • 材料化学

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