Letter abstract
Nature Cell Biology 10, 619 - 624 (2008)
Published online: 20 April 2008 | doi:10.1038/ncb1725
There is an Erratum (June 2008) associated with this Article.
Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells
Khalid Al-Nedawi1, Brian Meehan1, Johann Micallef3, Vladimir Lhotak2, Linda May2, Abhijit Guha3 & Janusz Rak1
Aggressive human brain tumours (gliomas) often express a truncated and oncogenic form of the epidermal growth factor receptor, known as EGFRvIII. Within each tumour only a small percentage of glioma cells may actually express EGFRvIII; however, most of the cells exhibit a transformed phenotype1. Here we show that EGFRvIII can be 'shared' between glioma cells by intercellular transfer of membrane-derived microvesicles ('oncosomes'). EGFRvIII expression in indolent glioma cells stimulates formation of lipid-raft related microvesicles containing EGFRvIII. Microvesicles containing this receptor are then released to cellular surroundings and blood of tumour-bearing mice, and can merge with the plasma membranes of cancer cells lacking EGFRvIII. This event leads to the transfer of oncogenic activity, including activation of transforming signalling pathways (MAPK and Akt), changes in expression of EGFRvIII-regulated genes (VEGF, Bcl-xL, p27), morphological transformation and increase in anchorage-independent growth capacity. Thus, membrane microvesicles of cancer cells can contribute to a horizontal propagation of oncogenes and their associated transforming phenotype among subsets of cancer cells.
- Montreal Children's Hospital Research Institute, McGill University, 4060 Ste Catherine West, Montreal, Quebec, Canada H3Z 2Z3.
- Henderson Research Centre, McMaster University, 711 Concession Street, Hamilton, Ontario, Canada, L8V 1C3.
- Arthur and Sonia Labatts Brain Tumor Centre, The Hospital for Sick Children, University of Toronto, TMDT-101 College Street, Toronto, Ontario, Canada M5G 1L7.
Correspondence to: Janusz Rak1 e-mail: janusz.rak@mcgill.ca
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
The Heregulin/Human Epidermal Growth Factor Receptor as a New Growth Factor System in Melanoma with Multiple Ways of DeregulationJournal of Investigative Dermatology Original Article
Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkersNature Cell Biology Letter (01 Dec 2008)
Intercellular transfer to signalling endosomes regulates an ex vivo bone marrow nicheNature Cell Biology Letter (01 Mar 2009)
