Circulating angiogenic cells in glioblastoma: toward defining crucial functional differences in CAC-induced neoplastic versus reactive neovascularization. Issue 1 (1st April 2020)

• Record Type: Journal Article
• Authors: Huizer, Karin; Sacchetti, Andrea; Swagemakers, Sigrid; van der Spek, Peter J; Dik, Wim; Mustafa, Dana A; Kros, Johan M
• Is Part Of: Neuro-oncology advances. Volume 2:Issue 1(2020)
• Publication Date: 2020-04-01
• Subjects: angiogenesis -- circulating angiogenic cell -- endothelial progenitor cell -- glioma -- hematopoietic progenitor cell -- myocardial infarction -- neovascularization; 616.99481
• DOI: 10.1093/noajnl/vdaa040
• Languages: English
• ISSNs: 2632-2498

Abstract

Abstract: Background: In order to identify suitable therapeutic targets for glioma anti-angiogenic therapy, the process of neovascularization mediated by circulating angiogenic cells (CACs) needs to be scrutinized. Methods: In the present study, we compared the expression of neovascularization-related genes by 3 circulating CAC subsets (hematopoietic progenitor cells [HPCs], CD34 +, and KDR + cells; internal controls: peripheral blood mononuclear cells and circulating endothelial cells) of treatment-naïve patients with glioblastoma (GBM) to those of patients undergoing reactive neovascularization (myocardial infarction (MI). CACs from umbilical cord (representing developmental neovascularization) and healthy subjects served as controls. Fluorescent-activated cell sorting was used to isolate CACs, RT-PCR to determine the expression levels of a panel of 48 neovascularization-related genes, and Luminex assays to measure plasma levels of 21 CAC-related circulating molecules. Results: We found essential differences in gene expression between GBM and MI CACs. GBM CACs had a higher expression of proangiogenic factors (especially, KITL, CXCL12, and JAG1 ), growth factor and chemotactic receptors ( IGF1R, TGFBR2, CXCR4, and CCR2 ), adhesion receptor monomers ( ITGA5 and ITGA6 ), and matricellular factor POSTN . In addition, we found major differences in the levels of neovascularization-related plasma factors. A strong positive correlation between plasma MMP9 levels and expression of CXCR4 in the CAC subset of HPCs was found in GBM patients. Conclusions: Our findings indicate that CAC-mediated neovascularization in GBM is characterized by more efficient CAC homing to target tissue and a more potent proangiogenic response than in physiologic tissue repair in MI. Our findings can aid in selecting targets for therapeutic strategies acting against GBM-specific CACs.