Abstract
Lymphangiogenesis refers to the formation of new lymphatic vessels and is thought to constitute conduits for the tumor cells to metastasize. We previously demonstrated that endothelin (ET)-1 through its binding with ETB receptor (ET(B)R) expressed on lymphatic endothelial cells (LEC), induced cell growth and invasiveness. Since vascular endothelial growth factor (VEGF)-A/-C/-D, and hypoxia play key role in lymphatic differentiation, in this study we investigated the involvement of these growth factors and hypoxia in ET-1-induced lymphangiogenesis. Real time PCR and ELISA were used to quantify VEGF-A/-C/-D. LEC morphological differentiation was analyzed by tube formation assay on Matrigel. Hypoxia, as well as ET-1, induced an increase in VEGF-A/-C and -D expression that was reduced in the presence of a selective ET(B)R antagonist, BQ788, and enhanced when ET-1 was administered under hypoxic conditions. We analyzed the role of hypoxia on LEC morphological differentiation, and found that hypoxia increased the formation of vascular-like structures on Matrigel and that in combination with ET-1 this effect was markedly enhanced. The use of specific antibodies neutralizing VEGF-A, or recombinant VEGFR-3/(Flt-4)/Fc that block VEGF-C/-D...Continue Reading
References
Jun 1, 1996·The Journal of Surgical Research·L B Reeder, M K Ferguson
Sep 5, 2001·The EMBO Journal·T MäkinenK Alitalo
May 25, 2002·The Journal of Biological Chemistry·Francesca SpinellaAnna Bagnato
Feb 4, 2003·Nature Reviews. Cancer·Joel NelsonPerry Nisen
Nov 2, 2005·Journal of Cellular Physiology·Emirena GarrafaArnaldo Caruso
Dec 16, 2005·Nature·Kari AlitaloTatiana V Petrova
Jan 21, 2006·Blood·Renhai CaoYihai Cao
Mar 15, 2006·Cancer Cell·Jen-Liang SuMin-Liang Kuo
Oct 5, 2006·Cancer Research·Yiping ZengElizabeth D Williams
Jan 11, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jeremy GoldmanMelody A Swartz
Apr 20, 2007·Biochimica Et Biophysica Acta·M IrigoyenA Rouzaut
Apr 27, 2007·Cellular and Molecular Life Sciences : CMLS·T MäkinenT V Petrova
Jul 13, 2007·Blood·Cornelia HalinMichael Detmar
Jul 20, 2007·Endocrine-related Cancer·M J Grimshaw
Oct 24, 2007·FEBS Letters·Hideki OtaMasaki Yanagishita
Dec 23, 2008·Blood·Shinae KangGou Young Koh
Mar 12, 2009·Cancer Research·Francesca SpinellaAnna Bagnato
Dec 8, 2009·Pflügers Archiv : European journal of physiology·Eric Thorin, David J Webb
Apr 22, 2010·Blood·Frederic Larrieu-LahargueDean Y Li
May 12, 2010·Current Molecular Medicine·M J VossF Entschladen
Jun 25, 2010·PloS One·Francesca SpinellaAnna Bagnato
Jul 10, 2010·The American Journal of Pathology·Leah N CueniMichael Detmar
Nov 30, 2010·Seminars in Oncology·Theresa Guise
Dec 7, 2010·Cancer Cell·Denis TvorogovKari Alitalo
Apr 12, 2011·Journal of Surgical Oncology·Marlys H WitteJeffrey E Gershenwald
Jun 30, 2011·The Biochemical Journal·Sina KochLena Claesson-Welsh
Aug 23, 2011·The International Journal of Developmental Biology·Imke Albrecht, Gerhard Christofori
Oct 11, 2011·The American Journal of Pathology·Mika SawaneKentaro Kajiya
Citations
Nov 15, 2012·BMC Cancer·Sarah PringelsJohan Grooten
Jul 26, 2013·Angiogenesis·Zerina LokmicAnthony J Penington
Jan 30, 2014·Carcinogenesis·Francesca SpinellaAnna Bagnato
Aug 29, 2014·Lymphatic Research and Biology·Yasumasa KakeiTakahide Komori
Sep 12, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Francesca SpinellaAnna Bagnato
Nov 2, 2015·Stem Cell Research·Maria NotaraC Cursiefen
Apr 16, 2014·The American Journal of Pathology·Junlan ZhangMichael B Fallon
Jan 23, 2014·Life Sciences·Mohammed AbdelsaidAdviye Ergul
Mar 13, 2014·Life Sciences·Valentina CapraraFrancesca Spinella
Jan 31, 2017·Lymphatic Research and Biology·Fabio TorriEmirena Garrafa
Jun 28, 2018·Physiological Research·W LiA Ergul