title: Autologous stem cell transplantation: leukapheresis product has anti-angiogenic effects in vivo correlating with neutrophil-derived VEGFR1.
abstract: BACKGROUND
  High-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT) is used for the treatment of hemato-oncologic malignancies. In this study, we measured the effect of HDC/ASCT on plasma concentrations of antiangiogenic soluble vascular endothelial growth factor receptor 1 (sVEGFR1) and of leukapheresis products (LP) and patient serum on chick chorioallantoic (CAM) angiogenesis.
  
  
  METHODS
  VEGFR1- and CD34-expressing cells of leukapheresis products were analyzed by flow cytometry. Alternatively spliced isoforms of VEGFR1 mRNA were quantified using reverse transcription PCR.
  
  
  RESULTS
  Plasma concentrations of sVEGFR1 decreased after HDC, but significantly increased after ASCT. In the CAM assay, sera of patients elicited a proangiogenic effect before and after HDC, but a strong antiangiogenic response after ASCT, comparable to that of bevacizumab at therapeutic concentrations. LP contains high concentrations of sVEGFR1, and high density of VEGFR1(+) neutrophilic granulocytes, in which mRNA expression is shifted toward the soluble VEGFR1 isoform.
  
  
  CONCLUSIONS
  Neutrophil-derived antiangiogenic sVEGFR1 within the LP may contribute to the therapeutic efficacy of ASCT.
authors.affiliation: Institute of Physiology and Zurich Center for Integrative Human Physiology ZIHP, University of Zurich, Zurich, Switzerland.
authors.forename: Anita
authors.initials: A
authors.lastname: Luethy
authors.forename: Frank
authors.initials: F
authors.lastname: Stenner
authors.forename: Corinne
authors.initials: C
authors.lastname: Lohri
authors.forename: Christoph
authors.initials: C
authors.lastname: Muller
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Samaras
authors.forename: Rudolf
authors.initials: R
authors.lastname: Steiner
authors.forename: Maries
authors.initials: M
authors.lastname: Van Den Broek
authors.forename: Axel
authors.initials: A
authors.lastname: Mischo
authors.forename: Christoph
authors.initials: C
authors.lastname: Renner
authors.forename: Alexander
authors.initials: A
authors.lastname: Knuth
authors.forename: Curzio
authors.initials: C
authors.lastname: Ruegg
authors.forename: Roland H
authors.initials: RH
authors.lastname: Wenger
authors.forename: Martin
authors.initials: M
authors.lastname: Zweifel
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007937:Leukapheresis; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012995:Solubility / Q000187:drug effects; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood* / Q000235:genetics
chemical_list: D020533:Angiogenesis Inhibitors; D018952:Antigens, CD34; D000970:Antineoplastic Agents; D012333:RNA, Messenger; D040281:Vascular Endothelial Growth Factor Receptor-1