Microfluidics and Nanofluidics

, Volume 14, Issue 6, pp 969–981 | Cite as

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
Research Paper

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.

Keywords

3D cell migration Microfluidics Anti-migratory drugs Interstitial flow 
2D

Two dimensional

HCC

Hepatocellular carcinoma

ART

Artemisinin

PDMS

Poly-dimethylsiloxane

VEGF

Vascular endothelial growth factor

bFGF

Basic fibroblast growth factor

HUVEC

Human umbilical vein endothelial cell

PBS

Phosphate-buffered saline

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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Johann Kalchman
    • 1
    • 3
  • Shingo Fujioka
    • 2
  • Seok Chung
    • 4
  • Yamato Kikkawa
    • 5
  • Toshihiro Mitaka
    • 6
  • Roger D. Kamm
    • 7
  • Kazuo Tanishita
    • 1
    • 2
  • Ryo Sudo
    • 1
    • 2
  1. 1.School of Integrated Design EngineeringKeio UniversityYokohamaJapan
  2. 2.Department of System Design EngineeringKeio UniversityYokohamaJapan
  3. 3.Ecole Centrale de LilleVilleneuve-d’AscqFrance
  4. 4.School of Mechanical EngineeringKorea UniversitySeoulKorea
  5. 5.Laboratory of Clinical BiochemistryTokyo University of Pharmacy and Life SciencesTokyoJapan
  6. 6.Department of Tissue Development and Regeneration, Research Institute for Frontier MedicineSapporo Medical University School of MedicineSapporoJapan
  7. 7.Departments of Mechanical Engineering and Biological EngineeringMassachusetts Institute of TechnologyCambridgeUSA

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