Three-dimensional extracellular matrix culture models of EGFR signalling and drug response.
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.
Kenny
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Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS 977-225A, University of California, Berkeley, CA 94720, USA. pakenny@lbl.gov
D066246:ErbB Receptors / Q000502:physiology*; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology*; D014407:Tumor Cells, Cultured
D066246:ErbB Receptors