Autologous Stem Cell Transplantation: Leukapheresis Product has Anti-angiogenic Effects In Vivo Correlating with Neutrophil-derived VEGFR1

作者：Luethy Anita^*; Stenner Frank; Lohri Corinne; Muller Christoph; Samaras Panagiotis; Steiner Rudolf; Van den Broek Maries; Mischo Axel; Renner Christoph; Knuth Alexander; Ruegg Curzio; Wenger Roland H; Zweifel Martin

来源：Anticancer Research, 2011, 31(10): 3115-3124.

• Alternative splicing
• angiogenesis
• autologous stem cell transplantation
• chick chorioallantoic membrane assay
• high-dose chemotherapy
• placental growth factor
• vascular endothelial growth factor
• VEGFR1

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 I (sVEGFR1) and of leukapheresis products (LP) and patient serum on chick chorioallantoic (CAM) angiogenesis. Materials and 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. Conclusion: Neutrophil-derived antiangiogenic sVEGFR1 within the LP may contribute to the therapeutic efficacy of ASCT.

• 出版日期2011-10