3D modeling of human cancer: A PEG-fibrin hydrogel system to study the role of tumor microenvironment and recapitulate the in vivo effect of oncolytic adenovirus

Francesca Del Bufalo, Teresa Manzo, Valentina Hoyos, Shigeki Yagyu, Ignazio Caruana, Jeffrey Jacot, Omar Benavides, Daniel Rosen, Malcolm K. Brenner

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Interactions between malignant and stromal cells and the 3D spatial architecture of the tumor both substantially modify tumor behavior, including the responses to small molecule drugs and biological therapies. Conventional 2D culture systems cannot replicate this complexity. To overcome these limitations and more accurately model solid tumors, we developed a highly versatile 3D PEG-fibrin hydrogel model of human lung adenocarcinoma. Our model relevantly recapitulates the effect of oncolytic adenovirus; tumor responses in this setting nearly reproduce those observed in vivo. We have also validated the use of this model for complex, long-term, 3D cultures of cancer cells and their stroma (fibroblasts and endothelial cells). Both tumor proliferation and invasiveness were enhanced in the presence of stromal components. These results validate our 3D hydrogel model as a relevant platform to study cancer biology and tumor responses to biological treatments.

Original languageEnglish (US)
Pages (from-to)76-85
Number of pages10
JournalBiomaterials
Volume84
DOIs
StatePublished - Apr 1 2016

Keywords

  • 3D tumor model
  • Oncolytic adenovirus
  • Preclinical drug testing
  • Tumor microenvironment

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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