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

Angiogenesis. 2013 Apr;16(2):405-16. doi: 10.1007/s10456-012-9323-8. Epub 2012 Nov 13.


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.

MeSH terms

  • AC133 Antigen
  • Antigens, CD / metabolism*
  • Apoptosis
  • Blotting, Western
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Glycoproteins / metabolism*
  • Humans
  • Immunohistochemistry
  • Melanoma / pathology
  • Peptides / metabolism*
  • Protein Binding
  • Real-Time Polymerase Chain Reaction
  • Vascular Endothelial Growth Factor A / metabolism*


  • AC133 Antigen
  • Antigens, CD
  • Glycoproteins
  • PROM1 protein, human
  • Peptides
  • Vascular Endothelial Growth Factor A