Enforced expression of KDR receptor promotes proliferation, survival and megakaryocytic differentiation of TF1 progenitor cell line

Ruggero De Maria Marchiano, S. Coppola, L. Narciso, T. Feccia, D. Bonci, L. Calabrò, O. Morsilli, M. Gabbianelli, U. Testa, Cesare Peschle

Risultato della ricerca: Contributo in rivistaArticolo in rivista

22 Citazioni (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) receptor-2/kinase insert domain-containing receptor (KDR) is expressed in primitive hematopoietic cells, in megakaryocytes and platelets. In primitive hematopoiesis KDR mediates cell survival via autocrine VEGF, while its effect on cell growth and differentiation has not been elucidated. We induced enforced KDR expression in the granulocyte macrophage-colony-stimulating factor (GM-CSF)-dependent TF1 progenitor cell line (TF1-KDR), treated the cells with VEGF and analyzed their response. In GM-CSF-deprived cells, VEGF induces cell proliferation and protection against apoptosis, followed by enhanced expression of megakaryocytic (MK) markers. Combined with GM-CSF, VEGF induces a mild proliferative stimulus, followed by cell adherence, accumulation in G0/G1, massive MK differentiation and Fas-mediated apoptosis. Accordingly, we observed that MK-differentiating cells, derived from hematopoietic progenitors, produce VEGF, express KDR, inhibition of which reduces MK differentiation, indicating a key role of KDR in megakaryopoiesis. In conclusion, TF1-KDR cells provide a reliable model to investigate the biochemical and molecular mechanisms underlying hematopoietic progenitor proliferation, survival and MK differentiation. © 2006 Nature Publishing Group. All rights reserved.
Lingua originaleEnglish
pagine (da-a)61-74
Numero di pagine14
RivistaCell Death and Differentiation
Volume13
DOI
Stato di pubblicazionePubblicato - 2006

Keywords

  • Adult
  • Apoptosis
  • Base Sequence
  • Cell Biology
  • Cell Differentiation
  • Cell Line
  • Cell Proliferation
  • Cell Survival
  • DNA
  • Gene Expression
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Hematopoietic Stem Cells
  • Hematopoietic progenitor
  • Humans
  • In Vitro Techniques
  • KDR
  • Male
  • Megakaryocyte
  • Megakaryocytes
  • Molecular Biology
  • Proliferation
  • Recombinant Proteins
  • Thrombopoiesis
  • VEGF
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-2

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