Institute of Physiology and Zurich Center for Integrative Human Physiology ZIHP, University of Zurich, Zurich, Switzerland.
Anticancer Res. 2011 Oct;31(10):3115-24.
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.
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.
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.
Neutrophil-derived antiangiogenic sVEGFR1 within the LP may contribute to the therapeutic efficacy of ASCT.
大剂量化疗（HDC）联合自体干细胞移植（ASCT）用于治疗血液系统恶性肿瘤。本研究旨在通过检测 HDC/ASCT 对血浆中可溶性血管内皮生长因子受体 1（sVEGFR1）浓度、白细胞分离术产物（LP）及患者血清对鸡胚尿囊膜（CAM）血管生成的影响，评估其疗效。
采用流式细胞术分析白细胞分离术产物中 VEGFR1 和 CD34 表达细胞，逆转录 PCR 定量检测不同剪接形式的 VEGFR1 mRNA。
HDC 后血浆 sVEGFR1 浓度降低，但 ASCT 后明显升高。CAM 检测结果显示，HDC 前后患者血清均具有促血管生成作用，但 ASCT 后呈强烈的抗血管生成反应，与贝伐单抗治疗浓度相当。LP 中含有高浓度的 sVEGFR1 和高表达的 VEGFR1（+）中性粒细胞，mRNA 表达偏向可溶性 VEGFR1 异构体。
LP 中的中性粒细胞来源的抗血管生成 sVEGFR1 可能有助于 ASCT 的治疗效果。
