Three-dimensional extracellular matrix culture models of EGFR signalling and drug response

Biochem Soc Trans. 2007 Aug;35(Pt 4):665-8. doi: 10.1042/BST0350665.


Three-dimensional extracellular matrix culture, on substrata such as Matrigel, restores many aspects of the differentiated state to non-malignant cells from a variety of tissues. We have adapted these techniques to study EGFR (epidermal growth factor receptor) signalling and drug response in breast cancer cell lines. EGFR-dependent breast cancer cell lines undergo a striking reversion of the malignant phenotype upon treatment with inhibitors targeting the receptor, or downstream signalling intermediates such as mitogen-activated protein kinase and PI3K (phosphoinositide 3-kinase). Using this approach, we have recently reported that EGFR signalling in breast cancer can be effectively inhibited by blocking the activity of a key protease, TACE [TNFalpha (tumour necrosis factor alpha)-converting enzyme], which regulates the bioavailability of EGFR ligands. These results suggest a new way to target EGFR signalling in tumours of the breast and other epithelial tissues and underline the value of three-dimensional extracellular matrix culture models for exploring cancer-relevant signalling processes ex vivo.

Publication types

  • Review

MeSH terms

  • ErbB Receptors / physiology*
  • Extracellular Matrix / drug effects*
  • Extracellular Matrix / metabolism*
  • Humans
  • Models, Biological*
  • Signal Transduction / physiology*
  • Tumor Cells, Cultured


  • ErbB Receptors