http://www.cnr.it/ontology/cnr/individuo/prodotto/ID26964
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)
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- Pagina fine
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- http://cancerres.aacrjournals.org/content/70/5/1804.long (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
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- 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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