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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)61-74
Number of pages14
JournalCell Death and Differentiation
Volume13
Issue number1
DOIs
Publication statusPublished - Jan 2006

Keywords

  • Hematopoietic progenitor
  • KDR
  • Megakaryocyte
  • Proliferation
  • VEGF

ASJC Scopus subject areas

  • Cell Biology

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    Coppola, S., Narciso, L., Feccia, T., Bonci, D., Calabrò, L., Morsilli, O., Gabbianelli, M., De Maria, R., Testa, U., & Peschle, C. (2006). Enforced expression of KDR receptor promotes proliferation, survival and megakaryocytic differentiation of TF1 progenitor cell line. Cell Death and Differentiation, 13(1), 61-74. https://doi.org/10.1038/sj.cdd.4401698