title: Vascular endothelial growth factor measured in platelet poor plasma allows optimal separation between cancer patients and volunteers: a key to study an angiogenic marker in vivo?
abstract: BACKGROUND
  Serum VEGF levels are elevated in cancer patients and are used as a tumor marker in different malignancies. We have measured VEGF levels in different blood compartments in cancer patients and healthy volunteers in order to assess the most suitable way of processing blood for measuring VEGF as a marker of tumor-angiogenesis.
  
  
  METHODS
  VEGF concentrations were analyzed by an enzyme-linked immunosorbent assay in serum (VEGFS), EDTA plasma (VEGFEDTA), citrated plasma (VEGFC), CTAD-plasma (VEGFCTAD), platelet poor plasma (VEGFPPP), platelet rich plasma after induction of platelet activation (VEGFPRP). Platelet activation was assessed by measuring PF4 concentrations in different plasma samples.
  
  
  RESULTS
  We observed higher VEGFS (P = 0.0027), VEGFEDTA (P = 0.003) and VEGFPPP (P = 0.0007) levels in cancer patients than in volunteers; VEGFPRP concentrations showed no significant difference (P = 0.208). Analysis of the correlation between VEGFplt and VEGFS in cancer patients showed a similar correlation in a comparable VEGFS concentration range as in the volunteers. When comparing VEGFC to VEGFCTAD, we find significantly higher VEGF and PF4 levels in citrated plasma (VEGF: P = 0.00019; PF4: P = 0.00023).
  
  
  CONCLUSIONS
  It is likely that VEGFS in cancer patients encompass platelet-delivered VEGF and VEGF from other sources, notably from (neo)-angiogenesis in tumoral tissue. The best discrimination between volunteers and cancer patients was observed in PPP. As generating plasma can induce platelet activation, with consequent VEGF release from platelets, we suggest that to assess free circulating VEGF, CTAD plasma should be used.
authors.affiliation: Laboratorium of Experimental Oncology, University Hospitals, Catholic University Leuven, Belgium.
authors.forename: W
authors.initials: W
authors.lastname: Wynendaele
authors.forename: R
authors.initials: R
authors.lastname: Derua
authors.forename: M F
authors.initials: MF
authors.lastname: Hoylaerts
authors.forename: A
authors.initials: A
authors.lastname: Pawinski
authors.forename: E
authors.initials: E
authors.lastname: Waelkens
authors.forename: E A
authors.initials: EA
authors.lastname: de Bruijn
authors.forename: R
authors.initials: R
authors.lastname: Paridaens
authors.forename: W
authors.initials: W
authors.lastname: Merlevede
authors.forename: A T
authors.initials: AT
authors.lastname: van Oosterom
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D016228:Endothelial Growth Factors / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000175:diagnosis*; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D014408:Biomarkers, Tumor; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors