Neurofibroma-associated growth factors activate a distinct signaling network to alter the function of neurofibromin-deficient endothelial cells

Human Molecular Genetics
Amy M MunchhofDavid A Ingram

Abstract

Genetic inactivation of tumor suppressor genes initiates human cancers. However, interaction of accessory cells with the tumor-initiating cell within the microenvironment is often required for tumor progression. This paradigm is relevant to understanding neurofibroma development in neurofibromatosis type I patients. Somatic inactivation of the Nf1 tumor suppressor gene, which encodes neurofibromin, is necessary but not sufficient to initiate neurofibroma development. In contrast, neurofibromas occur with high penetrance in mice in which Nf1 is ablated in Schwann cells in the context of a heterozygous mutant (Nf1+/-) microenvironment. Neurofibromas are highly vascularized, and recent studies suggest that Nf1+/- mice have increased angiogenesis in vivo. However, the function of neurofibromin in human endothelial cells (ECs) and the biochemical mechanism by which neurofibromin regulates neoangiogenesis are not known. Utilizing Nf1+/- mice, primary human ECs and endothelial progenitor cells harvested from NF1 patients, we identified a discrete Ras effector pathway, which alters the proliferation and migration of neurofibromin-deficient ECs in response to neurofibroma-derived growth factors both in vitro and in vivo. Thus, these stu...Continue Reading

References

May 2, 1991·The New England Journal of Medicine·V M Riccardi
Dec 16, 1993·Nature·M S Boguski, F McCormick
Nov 1, 1995·Trends in Biochemical Sciences·J L Bos
Dec 27, 1996·Cell·J Folkman, P A D'Amore
Apr 1, 1997·Molecular and Cellular Biology·P van der GeerT Pawson
Jun 19, 1998·Journal of the American Academy of Dermatology·J L ArbiserR L Barnhill
Aug 26, 1998·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·M M FeldkampA Guha
Sep 3, 1998·The Journal of Biological Chemistry·J YanJ F Hancock
Jan 5, 2000·The Journal of Clinical Investigation·Y LinR P Hebbel
Apr 14, 2000·International Journal of Molecular Medicine·B Larrivée, A Karsan
Nov 18, 2000·The Journal of Biological Chemistry·K K HiattD W Clapp
Mar 10, 2001·Cell·K Cichowski, T Jacks
Mar 30, 2001·The Journal of Biological Chemistry·A B Walsh, D Bar-Sagi
Apr 3, 2001·Trends in Pharmacological Sciences·M J Cross, L Claesson-Welsh
May 15, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Jianhua Huang, Christopher D Kontos
Oct 3, 2002·Nature Reviews. Cancer·Robert Kerbel, Judah Folkman
Dec 7, 2002·Nature Genetics·Aaron D GitlerJonathan A Epstein
Dec 20, 2002·Nature·Lisa M Coussens, Zena Werb
Jan 1, 2003·The American Journal of Pathology·Michael S GeeWilliam M F Lee
Feb 26, 2003·Genes & Development·Karen CichowskiTyler Jacks
Mar 15, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Yumei ZhanHiroshi Iwao
Jun 5, 2003·Cancer Cell·Kristian PietrasArne Ostman
Aug 9, 2003·Angiogenesis·R LongoG Gasparini
Aug 22, 2003·Experimental Dermatology·Yasuhiro KawachiFujio Otsuka
Dec 18, 2003·The Journal of Clinical Investigation·Feng-Chun YangD Wade Clapp
Mar 25, 2004·The American Journal of Pathology·Kelly HiattD Wade Clapp
Aug 26, 2004·Advances in Cancer Research·Brian J Druker
Nov 2, 2004·Nature Reviews. Cancer·Margareta M Mueller, Norbert E Fusenig
May 12, 2005·Angiogenesis·Ugur Ozerdem
Jun 7, 2005·Proceedings of the National Academy of Sciences of the United States of America·Cory M JohannessenKaren Cichowski
Jul 26, 2005·Biochimica Et Biophysica Acta·S J Plowman, J F Hancock

❮ Previous
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Citations

Jul 24, 2012·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Feng-Chun YangD Wade Clapp
Oct 10, 2012·Proceedings of the National Academy of Sciences of the United States of America·Hideto KosoNancy A Jenkins
Apr 23, 2011·Medicine·David MontaniFlorent Soubrier
Jun 24, 2010·Current Opinion in Hematology·Karl StaserDavid W Clapp
Feb 18, 2010·The Journal of Clinical Investigation·Elisabeth A LasaterDavid A Ingram
Jul 7, 2007·Neurosurgical Focus·Jonathan RileyNicholas Boulis
Sep 17, 2015·Pediatric Blood & Cancer·Michael J FergusonShi Chen
Nov 26, 2013·Clinics in Chest Medicine·Tim Lahm, Murali M Chakinala
Aug 20, 2009·Birth Defects Research. Part A, Clinical and Molecular Teratology·Vincent Michael Riccardi
Aug 2, 2007·American Journal of Human Genetics·Ophélia MaertensLudwine Messiaen
May 3, 2012·Stem Cells International·Araika Gutiérrez-RiveraAnder Izeta
Jul 18, 2014·Lancet Neurology·Angela C Hirbe, David H Gutmann
Nov 12, 2013·The American Journal of Pathology·Brian K StansfieldDavid A Ingram
Mar 18, 2010·Blood·Karl StaserD Wade Clapp
Sep 23, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Haiyan QinXiaofeng Huang
Aug 28, 2007·Journal of Cellular Biochemistry·S Sean Houshmandi, David H Gutmann
Aug 31, 2018·European Respiratory Review : an Official Journal of the European Respiratory Society·Etienne-Marie JutantDavid Montani
Jul 9, 2020·International Journal of Cancer. Journal International Du Cancer·Yoshihiro NishidaAkira Kawai
Feb 24, 2007·Human Molecular Genetics·Mateusz KolanczykStefan Mundlos
May 31, 2018·Investigative Ophthalmology & Visual Science·Hanfang ZhangBrian K Stansfield
Oct 12, 2021·Journal of Vascular Surgery. Venous and Lymphatic Disorders·Maria NuceraVladimir Makaloski

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