title: Castration resistant prostate cancer is associated with increased blood vessel stabilization and elevated levels of VEGF and Ang-2.
abstract: BACKGROUND
  Angiogenesis is important for the progression of prostate cancer and may be a target for treatment in castration resistant (CR) disease. This study was performed to investigate blood vessel stabilization and expression of the pro-angiogenic factors vascular endothelial growth factor (VEGF) and Angiopoietin-2 (Ang-2) in CR and hormone naïve (HN) prostate cancer. The effect of androgen deprivation therapy (ADT) on these parameters was also studied.
  
  
  METHODS
  VEGF and Ang-2, as well as pericyte coverage of blood vessels were studied in HN and CR prostate tumors by immunohistochemistry. The effects of ADT on VEGF expression and microvessel density (MVD) were investigated in biopsies at diagnosis, 3 months after starting ADT and at tumor relapse. Plasma was also analyzed for VEGF and Ang-2 with ELISA.
  
  
  RESULTS
  CR tumors had higher levels of VEGF and Ang-2 as well as increased blood vessel stabilization compared to HN tumors. Three months after initiated ADT an increase of VEGF but not MVD in the tumors was observed. In contrast, plasma levels of VEGF decreased after ADT, and increased again at time of tumor relapse. Ang-2 levels were unaffected.
  
  
  CONCLUSIONS
  CR prostate cancer is associated with elevated levels of VEGF and Ang-2, indicating that these factors could be used as targets for anti-angiogenic treatment. Still, the observed increase in blood vessel stabilization in CR tumors could influence the outcome of anti-angiogenic treatment. Furthermore, increased VEGF expression after 3 months of ADT justifies the use of VEGF-based anti-angiogenic drugs in combination with ADT for the treatment of advanced prostate cancer.
authors.affiliation: Sahlgrenska Cancer Center, Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden.
authors.forename: Tajana Tešan
authors.initials: TT
authors.lastname: Tomić
authors.forename: Heléne
authors.initials: H
authors.lastname: Gustavsson
authors.forename: Wanzhong
authors.initials: W
authors.lastname: Wang
authors.forename: Karin
authors.initials: K
authors.lastname: Jennbacken
authors.forename: Karin
authors.initials: K
authors.lastname: Welén
authors.forename: Jan-Erik
authors.initials: JE
authors.lastname: Damber
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D042702:Angiopoietin-2 / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000097:blood / Q000378:metabolism; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000601:surgery; D042461:Vascular Endothelial Growth Factor A / Q000097:blood* / Q000378:metabolism
chemical_list: D042702:Angiopoietin-2; D042461:Vascular Endothelial Growth Factor A