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Angiogenesis

, Volume 16, Issue 2, pp 405–416 | Cite as

The stem cell marker prominin-1/CD133 interacts with vascular endothelial growth factor and potentiates its action

  • Avner AdiniEmail author
  • Irit Adini
  • Kaustabh Ghosh
  • Ofra Benny
  • Elke Pravda
  • Ron Hu
  • Dema Luyindula
  • Robert J. D’Amato
Original Paper

Abstract

Prominin-1, a pentaspan transmembrane protein, is a unique cell surface marker commonly used to identify stem cells, including endothelial progenitor cells and cancer stem cells. However, recent studies have shown that prominin-1 expression is not restricted to stem cells but also occurs in modified forms in many mature adult human cells. Although prominin-1 has been studied extensively as a stem cell marker, its physiological function of the protein has not been elucidated. We investigated prominin-1 function in two cell lines, primary human endothelial cells and B16-F10 melanoma cells, both of which express high levels of prominin-1. We found that prominin-1 directly interacts with the angiogenic and tumor survival factor vascular endothelial growth factor (VEGF) in both the primary endothelial cells and the melanoma cells. Knocking down prominin-1 in the endothelial cells disrupted capillary formation in vitro and decreased angiogenesis in vivo. Similarly, tumors derived from prominin-1 knockdown melanoma cells had a reduced growth rate in vivo. Further, melanoma cells with knocked down prominin-1 had diminished ability to interact with VEGF, which was associated with decreased bcl-2 protein levels and increased apoptosis. In vitro studies with soluble prominin-1 showed that it stabilized dimer formation of VEGF164, but not VEGF121. Taken together, our findings support the notion that prominin-1 plays an active role in cell growth through its ability to interact and potentiate the anti-apoptotic and pro-angiogenic activities of VEGF. Additionally, prominin-1 promotes tumor growth by supporting angiogenesis and inhibiting tumor cell apoptosis.

Keywords

Prominin-1 CD133 Vascular endothelial growth factor Apoptosis melanoma 

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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Avner Adini
    • 1
    Email author
  • Irit Adini
    • 1
  • Kaustabh Ghosh
    • 3
  • Ofra Benny
    • 1
  • Elke Pravda
    • 1
  • Ron Hu
    • 1
  • Dema Luyindula
    • 1
  • Robert J. D’Amato
    • 1
    • 2
  1. 1.Vascular Biology Program, Department of Surgery, Children’s HospitalHarvard Medical SchoolBostonUSA
  2. 2.Department of OphthalmologyHarvard Medical SchoolBostonUSA
  3. 3.Department of BioengineeringUniversity of California-RiversideRiversideUSA

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