title: Peptides binding to prostate-specific antigen enhance its antiangiogenic activity.
abstract: BACKGROUND
  Proteolytically active prostate-specific antigen (PSA or kallikrein-related peptidase 3, KLK3) has been shown to exert antiangiogenic properties. High levels of PSA in prostatic tumors may thus slow down cancer progression by inhibiting angiogenesis. We hypothesize that factors stimulating the activity of PSA could be used to reduce prostate tumor growth. Using phage display, we have developed peptides C4 and B2 that stimulate the enzymatic activity of PSA. Our aim was to study whether these peptides enhance the antiangiogenic activity of PSA.
  
  
  METHODS
  We used an in vitro angiogenesis assay where human umbilical vein endothelial cells (HUVECs) form tubular networks when they are grown on Matrigel. Proteolytically active PSA and peptides that stimulate the activity of PSA were added to the cells. Endothelial cell tube formation was quantified and expressed as an angiogenesis index.
  
  
  RESULTS
  PSA reduced the angiogenesis index to ∼50% of controls both in serum-containing and serum-free medium. The addition of peptide C4 or B2 together with PSA caused a significant further decrease in angiogenesis index to ∼70% of that caused by PSA alone. A similar decrease in angiogenesis index was observed when PSA concentration was increased 2.4-fold of that used with peptides.
  
  
  CONCLUSIONS
  The inhibitory effect of PSA on tube formation can be enhanced by the addition of peptides that stimulate the activity of PSA. This supports our hypothesis that stimulation of PSA activity can be used to reduce angiogenesis and thereby inhibit prostate tumor growth.
authors.affiliation: Department of Clinical Chemistry, Biomedicum Helsinki, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Mattsson
authors.forename: Ale
authors.initials: A
authors.lastname: Närvänen
authors.forename: Ulf-Håkan
authors.initials: UH
authors.lastname: Stenman
authors.forename: Hannu
authors.initials: H
authors.lastname: Koistinen
mesh_terms: D004305:Dose-Response Relationship, Drug; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D008297:Male; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology*; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000378:metabolism; D018709:Statistics, Nonparametric
chemical_list: D010456:Peptides, Cyclic; D017430:Prostate-Specific Antigen