3D Coculture Models Underline Metastatic Melanoma Cell Sensitivity to Vemurafenib

Tissue Eng Part A. 2019 Aug;25(15-16):1116-1126. doi: 10.1089/ten.TEA.2018.0210. Epub 2019 Jan 18.

Abstract

Three dimensional in vitro cell culture systems better reflect the native structural architecture of tissues and are attractive to investigate cancer cell sensitivity to drugs. We have developed and compared several metastatic melanoma (MM) models cultured as a monolayer (2D) and cocultured on three dimensional (3D) dermal equivalents with fibroblasts to better unravel factors modulating cell sensitivity to vemurafenib, a BRAF inhibitor. The heterotypic 3D melanoma model we have established summarizes paracrine signalization by stromal cells and type I collagen matrix, mimicking the natural microenvironment of cutaneous MM, and allows for the identification of potent sensitive melanoma cells to the drug. This model could be a powerful tool for predicting drug efficiency.

Keywords: 3D human melanoma model; BRAFi efficiency; targeted therapy; tissue engineering; tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Coculture Techniques*
  • Culture Media, Conditioned / pharmacology
  • Dermis / pathology
  • Fibroblasts / drug effects
  • Humans
  • Melanoma / pathology*
  • Neoplasm Metastasis
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf / metabolism
  • Signal Transduction / drug effects
  • Solubility
  • Tumor Microenvironment / drug effects
  • Vemurafenib / pharmacology*

Substances

  • Culture Media, Conditioned
  • Protein Kinase Inhibitors
  • Vemurafenib
  • Proto-Oncogene Proteins B-raf