Syndecan-1 promotes the angiogenic phenotype of multiple myeloma endothelial cells

Leukemia. 2012 May;26(5):1081-90. doi: 10.1038/leu.2011.290. Epub 2011 Oct 25.

Abstract

Angiogenesis is considered a hallmark of multiple myeloma (MM) progression. In the present study, we evaluated the morphological and functional features of endothelial cells (ECs) derived from bone marrow (BM) of patients affected by MM (MMECs). We found that MMECs compared with normal BM ECs (BMECs) showed increased expression of syndecan-1. Silencing of syndecan-1 expression by RNA interference technique decreased in vitro EC survival, proliferation and organization in capillary-like structures. In vivo, in severe combined immunodeficient mice, syndecan-1 silencing inhibited MMEC organization into patent vessels. When overexpressed in human umbilical vein ECs and BMECs, syndecan-1 induced in vitro and in vivo angiogenic effects. Flow-cytometric analysis of MMECs silenced for syndecan-1 expression indicated a decreased membrane expression of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2). Immunoprecipitation and confocal analysis showed colocalization of VEGFR-2 with syndecan-1. Absence of nuclear translocation of VEGFR-2 in syndecan-1-knockdown cells together with the shift from perinuclear localization to recycling compartments suggest a role of syndecan-1 in modulation of VEGFR-2 localization. This correlated with an in vitro decreased VEGF-induced invasion and motility. These results suggest that syndecan-1 may contribute to the highly angiogenic phenotype of MMECs by promoting EC proliferation, survival and modulating VEGF-VEGFR-2 signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Endothelium / pathology*
  • Flow Cytometry
  • Gene Silencing
  • Humans
  • Immunoprecipitation
  • Mice
  • Multiple Myeloma / blood supply
  • Multiple Myeloma / pathology*
  • Neovascularization, Pathologic*
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction
  • Syndecan-1 / genetics
  • Syndecan-1 / physiology*
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Syndecan-1
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-2