Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells

Nature Cell Biology
Khalid Al-NedawiJanusz Rak

Abstract

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 phenotype. 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-x(L), 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.

References

Mar 17, 1999·International Journal of Cancer. Journal International Du Cancer·M M FeldkampA Guha
May 17, 2001·Proceedings of the National Academy of Sciences of the United States of America·A BergsmedhL Holmgren
May 18, 2001·Nature·P Blume-Jensen, T Hunter
May 23, 2002·Carcinogenesis·Webster K Cavenee
Jun 15, 2004·Brain Pathology·Wojciech BiernatHiroko Ohgaki
Oct 23, 2004·International Journal of Cancer. Journal International Du Cancer·Anna Janowska-WieczorekMariusz Z Ratajczak
May 28, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·Khalid Al-NedawiCzeslaw S Cierniewski
Sep 29, 2005·Springer Seminars in Immunopathology·David PilzerZvi Fishelson
May 3, 2006·Cancer Research·Xin YuArnold J Levine

❮ Previous
Next ❯

Citations

May 12, 2011·Cellular and Molecular Life Sciences : CMLS·Bence GyörgyEdit I Buzás
Feb 4, 2009·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Costas G Hadjipanayis, Erwin G Van Meir
Mar 23, 2013·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Christoph Kahlert, Raghu Kalluri
Jun 21, 2011·Seminars in Immunopathology·Douglas D Taylor, Cicek Gercel-Taylor
Feb 19, 2013·Bulletin of Mathematical Biology·Yasir SuhailAndre Levchenko
May 16, 2012·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Ruowen GeHarry H Asada
Dec 15, 2010·Langmuir : the ACS Journal of Surfaces and Colloids·Lie Na TanNicholas L Abbott
Aug 24, 2011·Journal of Proteome Research·Bianca S BatistaLara K Mahal
Sep 3, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Xandra O BreakefieldRichard J Simpson
Aug 23, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Arda MizrakOkay Saydam
Jan 25, 2013·Molecular Therapy. Nucleic Acids·Mehmet Fatih BolukbasiOkay Saydam
Feb 10, 2009·Nature Cell Biology·Jennifer M GilletteJennifer Lippincott-Schwartz
Jun 5, 2012·Nature Cell Biology·Maria Francesca BaiettiGuido David
Feb 3, 2011·Nature Communications·Leonora BalajJohan Skog
Apr 16, 2013·Nature Reviews. Drug Discovery·Samir EL AndaloussiMatthew J A Wood
Jun 6, 2009·Nature Reviews. Immunology·Clotilde ThéryElodie Segura
Feb 24, 2009·Proceedings of the National Academy of Sciences of the United States of America·Khalid Al-NedawiJanusz Rak
Mar 4, 2011·Proceedings of the National Academy of Sciences of the United States of America·Marc A AntonyakRichard A Cerione
Jul 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Katrin J SvenssonMattias Belting
Apr 17, 2013·Proceedings of the National Academy of Sciences of the United States of America·Paulina KucharzewskaMattias Belting
Apr 1, 2010·The Journal of Biological Chemistry·Nobuyoshi KosakaTakahiro Ochiya
Mar 23, 2012·The Journal of Biological Chemistry·Kate KolesVivian Budnik
Oct 5, 2010·Journal of Neurotrauma·John B RedellPramod K Dash
Apr 12, 2011·Thyroid : Official Journal of the American Thyroid Association·Matthew D Ringel
May 1, 2013·Molecular Biology of the Cell·David A ShifrinMatthew J Tyska
Jul 10, 2012·Nucleic Acids Research·Jaime PalmaDominik M Duelli
Dec 26, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Michael W GranerDarell D Bigner
Nov 21, 2012·Current Opinion in Oncology·Vilma R MartinsPierre Hainaut
Jul 17, 2009·Current Opinion in Hematology·Pavel Davizon, José A López
Aug 27, 2010·Current Opinion in Hematology·Joseph E ItalianoRobert Flaumenhaft

❮ Previous
Next ❯

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Khalid Al-NedawiJanusz Rak
Trends in Cell Biology
Emanuele CocucciJacopo Meldolesi
Proceedings of the National Academy of Sciences of the United States of America
Marc A AntonyakRichard A Cerione
© 2022 Meta ULC. All rights reserved