Three-dimensional culture systems in cancer research: Focus on tumor spheroid model

Pharmacol Ther. 2016 Jul:163:94-108. doi: 10.1016/j.pharmthera.2016.03.013. Epub 2016 Apr 8.


Cancer cells propagated in three-dimensional (3D) culture systems exhibit physiologically relevant cell-cell and cell-matrix interactions, gene expression and signaling pathway profiles, heterogeneity and structural complexity that reflect in vivo tumors. In recent years, development of various 3D models has improved the study of host-tumor interaction and use of high-throughput screening platforms for anti-cancer drug discovery and development. This review attempts to summarize the various 3D culture systems, with an emphasis on the most well characterized and widely applied model - multicellular tumor spheroids. This review also highlights the various techniques to generate tumor spheroids, methods to characterize them, and its applicability in cancer research.

Keywords: Apoptosis; High-throughput screening; Inflammatory breast cancer; Invasion; Oxidative stress; Tumor emboli.

Publication types

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

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Communication / physiology*
  • Cell Culture Techniques / methods*
  • Cell Movement / physiology
  • Flow Cytometry
  • Humans
  • Hydrogels / chemistry
  • Microscopy, Confocal
  • Microscopy, Electron, Scanning
  • Neoplasm Invasiveness / physiopathology
  • Neoplasms / physiopathology*
  • Spheroids, Cellular / physiology*
  • Tumor Cells, Cultured
  • Tumor Microenvironment / physiology


  • Antineoplastic Agents
  • Hydrogels