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Pleiotrophin selectively binds to vascular endothelial growth factor receptor 2 and inhibits or stimulates cell migration depending on ανß3 integrin expression.
Lamprou, Margarita; Kastana, Pinelopi; Kofina, Fani; Tzoupis, Ηaralampos; Barmpoutsi, Spyridoula; Sajib, Md Sanaullah; Koutsioumpa, Marina; Poimenidi, Evangelia; Zompra, Aikaterini A; Tassopoulos, Dimitrios; Choleva, Effrosyni; Tselios, Theodore; Mikelis, Constantinos M; Papadimitriou, Evangelia.
Afiliación
  • Lamprou M; Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, 26504, Patras, Greece.
  • Kastana P; Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, 26504, Patras, Greece.
  • Kofina F; Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, 26504, Patras, Greece.
  • Tzoupis Η; Department of Chemistry, University of Patras, Patras, Greece.
  • Barmpoutsi S; Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, 26504, Patras, Greece.
  • Sajib MS; Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA.
  • Koutsioumpa M; Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, 26504, Patras, Greece.
  • Poimenidi E; Center for Systems Biomedicine, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Zompra AA; Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, 26504, Patras, Greece.
  • Tassopoulos D; Dual Training in Intensive Care Medicine and Anaesthesia, Glenfield General Hospital, University Hospitals of Leicester NHS Trust, Groby Road, Leicester, LE3 9QP, UK.
  • Choleva E; Laboratory of Pharmacognosy and Chemistry of Natural Products, Department of Pharmacy, University of Patras, 26504, Patras, Greece.
  • Tselios T; Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, 26504, Patras, Greece.
  • Mikelis CM; Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, 26504, Patras, Greece.
  • Papadimitriou E; Department of Chemistry, University of Patras, Patras, Greece.
Angiogenesis ; 23(4): 621-636, 2020 11.
Article en En | MEDLINE | ID: mdl-32681389
Pleiotrophin (PTN) has a moderate stimulatory effect on endothelial cell migration through ανß3 integrin, while it decreases the stimulatory effect of vascular endothelial growth factor A (VEGFA) and inhibits cell migration in the absence of ανß3 through unknown mechanism(s). In the present work, by using a multitude of experimental approaches, we show that PTN binds to VEGF receptor type 2 (VEGFR2) with a KD of 11.6 nM. Molecular dynamics approach suggests that PTN binds to the same VEGFR2 region with VEGFA through its N-terminal domain. PTN inhibits phosphorylation of VEGFR2 at Tyr1175 and still stimulates endothelial cell migration in the presence of a selective VEGFR2 tyrosine kinase inhibitor. VEGFR2 downregulation by siRNA or an anti-VEGFR2 antibody that binds to the ligand-binding VEGFR2 domain also induce endothelial cell migration, which is abolished by a function-blocking antibody against ανß3 or the peptide PTN112-136 that binds ανß3 and inhibits PTN binding. In cells that do not express ανß3, PTN decreases both VEGFR2 Tyr1175 phosphorylation and cell migration in a VEGFR2-dependent manner. Collectively, our data identify VEGFR2 as a novel PTN receptor involved in the regulation of cell migration by PTN and contribute to the elucidation of the mechanism of activation of endothelial cell migration through the interplay between VEGFR2 and ανß3.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Portadoras / Movimiento Celular / Citocinas / Receptor 2 de Factores de Crecimiento Endotelial Vascular / Integrina alfaVbeta3 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Angiogenesis Asunto de la revista: HEMATOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Grecia Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Portadoras / Movimiento Celular / Citocinas / Receptor 2 de Factores de Crecimiento Endotelial Vascular / Integrina alfaVbeta3 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Angiogenesis Asunto de la revista: HEMATOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Grecia Pais de publicación: Alemania