A Microdevice Platform Recapitulating Hypoxic Tumor Microenvironments

Sci Rep. 2017 Nov 9;7(1):15233. doi: 10.1038/s41598-017-15583-3.

Abstract

Hypoxia plays a central role in cancer progression and resistance to therapy. We have engineered a microdevice platform to recapitulate the intratumor oxygen gradients that drive the heterogeneous hypoxic landscapes in solid tumors. Our design features a "tumor section"-like culture by incorporating a cell layer between two diffusion barriers, where an oxygen gradient is established by cellular metabolism and physical constraints. We confirmed the oxygen gradient by numerical simulation and imaging-based oxygen sensor measurement. We also demonstrated spatially-resolved hypoxic signaling in cancer cells through immunostaining, gene expression assay, and hypoxia-targeted drug treatment. Our platform can accurately generate and control oxygen gradients, eliminates complex microfluidic handling, allows for incorporation of additional tumor components, and is compatible with high-content imaging and high-throughput applications. It is well suited for understanding hypoxia-mediated mechanisms in cancer disease and other biological processes, and discovery of new therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytological Techniques / instrumentation*
  • Cytological Techniques / methods*
  • Gene Expression Profiling
  • Humans
  • Hypoxia*
  • Immunohistochemistry
  • MCF-7 Cells
  • Neoplasms / pathology*
  • Oxygen / analysis
  • Tumor Microenvironment*

Substances

  • Oxygen