A placental growth factor variant unable to recognize vascular endothelial growth factor (VEGF) receptor-1 inhibits VEGF-dependent tumor angiogenesis via heterodimerization (Articolo in rivista)

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  • A placental growth factor variant unable to recognize vascular endothelial growth factor (VEGF) receptor-1 inhibits VEGF-dependent tumor angiogenesis via heterodimerization (Articolo in rivista) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1158/0008-5472.CAN-09-2609 (literal)
Alternative label
  • Tarallo V.; Vesci L.; Capasso O.; Esposito M.T.; Riccioni T.; Pastore L.; Orlandi A.; Pisano C. and De Falco S. (2010)
    A placental growth factor variant unable to recognize vascular endothelial growth factor (VEGF) receptor-1 inhibits VEGF-dependent tumor angiogenesis via heterodimerization
    in Cancer research (Chic. Ill.); American Association For Cancer Research, Philadelphia (Stati Uniti d'America)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Tarallo V.; Vesci L.; Capasso O.; Esposito M.T.; Riccioni T.; Pastore L.; Orlandi A.; Pisano C. and De Falco S. (literal)
Pagina inizio
  • 1804 (literal)
Pagina fine
  • 1813 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url
  • http://cancerres.aacrjournals.org/content/70/5/1804.long (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 70 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#note
  • PMID: 20145150 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 5 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Angiogenesis Lab and Stem Cell Fate Lab, Institute of Genetics and Biophysics \"Adriano Buzzati-Traverso,\" CNR, Napoli, Italy Centro di Ricerca per l'Ingegneria Genetica-Biotecnologie Avanzate; Napoli, Italy Department of Biochemistry and Medical Biotechnology, University of Naples \"Federico II,\" Naples, Italy Research and Development Oncology Area, Sigma-Tau S.p.A., Industrie Farmaceutiche Riunite; Pomezia (Roma), Italy Anatomic Pathology Institute, Department of Biopathology and Image Diagnostics, Tor Vergata University, Roma, Italy (literal)
Titolo
  • A placental growth factor variant unable to recognize vascular endothelial growth factor (VEGF) receptor-1 inhibits VEGF-dependent tumor angiogenesis via heterodimerization (literal)
Abstract
  • Angiogenesis is one of the crucial events for cancer development and growth. Two members of the vascular endothelial growth factor (VEGF) family, VEGF-A and placental growth factor (PlGF), which are able to heterodimerize if coexpressed in the same cell, are both required for pathologic angiogenesis. We have generated a PlGF1 variant, named PlGF1-DE in which the residues Asp72 and Glu73 were substituted with Ala, which is unable to bind and activate VEGF receptor-1 but is still able to heterodimerize with VEGF. Here, we show that overexpression in tumor cells by adenoviral delivery or stable transfection of PlGF1-DE variant significantly reduces the production of VEGF homodimer via heterodimerization, determining a strong inhibition of xenograft tumor growth and neoangiogenesis, as well as significant reduction of vessel lumen and stabilization, and monocyte-macrophage infiltration. Conversely, the overexpression of PlGF1wt, also reducing the VEGF homodimer production comparably with PlGF1-DE variant through the generation of VEGF/PlGF heterodimer, does not inhibit tumor growth and vessel density compared with controls but induces increase of vessel lumen, vessel stabilization, and monocyte-macrophage infiltration. The property of PlGF and VEGF-A to generate heterodimer represents a successful strategy to inhibit VEGF-dependent angiogenesis. The PlGF1-DE variant, and not PlGF1wt as previously reported, acts as a \"dominant negative\" of VEGF and is a new candidate for antiangiogenic gene therapy in cancer treatment. (literal)
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