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

被引:0
|
作者
Luethy, Anita [1 ,2 ]
Stenner, Frank [3 ]
Lohri, Corinne [3 ]
Muller, Christoph [1 ,2 ]
Samaras, Panagiotis [3 ]
Steiner, Rudolf [3 ]
Van den Broek, Maries [3 ]
Mischo, Axel [3 ]
Renner, Christoph [3 ]
Knuth, Alexander [3 ]
Ruegg, Curzio [4 ]
Wenger, Roland H. [1 ,2 ]
Zweifel, Martin [3 ]
机构
[1] Univ Zurich, Inst Physiol, Zurich, Switzerland
[2] Univ Zurich, Zurich Ctr Integrat Human Physiol ZIHP, Zurich, Switzerland
[3] Univ Zurich Hosp, Dept Oncol, CH-8091 Zurich, Switzerland
[4] Univ Fribourg, Fac Sci, Dept Med, CH-1700 Fribourg, Switzerland
关键词
Alternative splicing; angiogenesis; autologous stem cell transplantation; chick chorioallantoic membrane assay; high-dose chemotherapy; placental growth factor; vascular endothelial growth factor; VEGFR1; ENDOTHELIAL GROWTH-FACTOR; BONE-MARROW-TRANSPLANTATION; ACUTE MYOCARDIAL-INFARCTION; PERIPHERAL-BLOOD; PROGENITOR CELLS; MULTIPLE-MYELOMA; FACTOR RECEPTOR-1; TYROSINE KINASE; LIMB ISCHEMIA; THERAPEUTIC ANGIOGENESIS;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页码:3115 / 3124
页数:10
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