Inhibition of solid tumor growth by gene transfer of VEGF receptor-1 mutants

International Journal of Cancer. Journal International Du Cancer
Regina HeidenreichGeorg Breier

Abstract

Vascular endothelial growth factor (VEGF) and the high-affinity VEGF receptor Flk-1/KDR (VEGFR-2) are key regulators of tumor angiogenesis. Strategies to block VEGF/VEGFR-2 signaling were successfully used to inhibit experimental tumor growth and indicated that VEGFR-2 is the main signaling VEGF receptor in proliferating tumor endothelium. Here, we investigated the role of the VEGF receptor-1 (VEGFR-1/Flt-1) in the vascularization of 2 different experimental tumors in vivo. VEGFR-1 mutants were generated that lack the intracellular tyrosine kinase domain. Retrovirus-mediated gene transfer of the VEGFR-1 mutants led to a strong reduction of tumor growth and angiogenesis in xenografted C6 glioma and in syngeneic BFS-1 fibrosarcoma. Histological analysis of the inhibited fibrosarcoma revealed reduced vascular density, decreased tumor cell proliferation as well as increased tumor cell apoptosis and the formation of necrosis. The retroviral gene transfer of the full length VEGFR-1 also caused a significant reduction of tumor growth in both models. The inhibitory effects of the VEGFR-1 mutants and the full length VEGFR-1 in BFS-1 fibrosarcoma were mediated through host tumor endothelial cells because the BFS-1 fibrosarcoma cells were...Continue Reading

References

Aug 1, 1987·Molecular and Cellular Biology·C Chen, H Okayama
Aug 12, 1971·The New England Journal of Medicine·J Folkman
Nov 7, 1995·Proceedings of the National Academy of Sciences of the United States of America·L P AielloL E Smith
Nov 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·R L Kendall, K A Thomas
Jan 1, 1995·Breast Cancer Research and Treatment·N Ferrara
Nov 1, 1995·Developmental Dynamics : an Official Publication of the American Association of Anatomists·G BreierW Risau
May 3, 1996·International Journal of Cancer. Journal International Du Cancer·M HafnerD N Männel
Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·S Y ChengW K Cavenee
Dec 17, 1997·Biochemical and Biophysical Research Communications·S A CunninghamM N Waxham
Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·C K GoldmanD T Curiel
Aug 5, 1998·Proceedings of the National Academy of Sciences of the United States of America·S HiratsukaM Shibuya
Jan 20, 1999·Current Topics in Microbiology and Immunology·N Ferrara
Apr 11, 2000·Gene Therapy·T AsaharaJ M Isner
May 10, 2000·The Oncologist·G McMahon
Dec 29, 2000·Seminars in Thrombosis and Hemostasis·G Breier
Mar 14, 2001·Journal of Neuro-oncology·M R Machein, K H Plate
Apr 20, 2001·The International Journal of Biochemistry & Cell Biology·M Shibuya
Oct 5, 2001·Cellular Signalling·N ItoL Claesson-Welsh

❮ Previous
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Citations

Mar 25, 2006·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Alexandra GiatromanolakiUNKNOWN Tumour and Angiogenesis Research Group
Feb 19, 2010·Human Gene Therapy·Haritha SamaranayakeSeppo Ylä-Herttuala
Sep 26, 2013·Advanced Drug Delivery Reviews·Yu ChengMaciej S Lesniak
Aug 22, 2012·Neuroscience Letters·NaTosha N GatsonBalveen Kaur
Jan 5, 2006·Brain Pathology·Jean-Pierre GagnerDavid Zagzag
Jan 19, 2007·International Journal of Cancer. Journal International Du Cancer·Jens GilleGeorg Breier
Aug 4, 2006·Journal of Controlled Release : Official Journal of the Controlled Release Society·Won Jong KimSung Wan Kim
Sep 29, 2017·Nanomedicine·Fatemeh MovahediZhi Ping Xu
Jun 11, 2005·The Journal of Biological Chemistry·Sonia Mulero-NavarroPedro M Fernández-Salguero
Jan 5, 2006·Brain Pathology·Ingeborg FischerDavid Zagzag
Sep 3, 2005·Cancer Gene Therapy·S E LawlerE A Chiocca
Oct 14, 2017·The Journal of Pharmacology and Experimental Therapeutics·Maria Grazia AtzoriGrazia Graziani
Mar 23, 2005·Cancer Research·Arati SharmaGavin P Robertson
Oct 6, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hidenobu IshizakiHideaki Tahara
Apr 2, 2021·Frontiers in Molecular Neuroscience·Kaushik BanerjeeMaria G Castro
Aug 28, 2021·Brain Sciences·Alice Giotta Lucifero, Sabino Luzzi

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