title: The stem cell marker prominin-1/CD133 interacts with vascular endothelial growth factor and potentiates its action.
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.
authors.affiliation: Vascular Biology Program, Department of Surgery, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. avner.adini@childrens.harvard.edu
authors.forename: Avner
authors.initials: A
authors.lastname: Adini
authors.forename: Irit
authors.initials: I
authors.lastname: Adini
authors.forename: Kaustabh
authors.initials: K
authors.lastname: Ghosh
authors.forename: Ofra
authors.initials: O
authors.lastname: Benny
authors.forename: Elke
authors.initials: E
authors.lastname: Pravda
authors.forename: Ron
authors.initials: R
authors.lastname: Hu
authors.forename: Dema
authors.initials: D
authors.lastname: Luyindula
authors.forename: Robert J
authors.initials: RJ
authors.lastname: D'Amato
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis; D015153:Blotting, Western; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000473:pathology; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D060888:Real-Time Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A