Circulating angiogenic cells in glioblastoma: Toward defining crucial functional differences in CAC-induced neoplastic versus reactive neovascularization

Karin Huizer, Andrea Sacchetti, Sigrid Swagemakers, Peter J. Van Der Spek, Wim Dik, Dana A. Mustafa, Johan M. Kros*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)
10 Downloads (Pure)

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.

Original languageEnglish
Article numbervdaa040
JournalNeuro-Oncology Advances
Volume2
Issue number1
DOIs
Publication statusPublished - 1 Jan 2020

Bibliographical note

Funding:
The funding for this project was provided by the Department of
Pathology of the Erasmus Medical Center.

Publisher Copyright:
© 2020 The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.

Fingerprint

Dive into the research topics of 'Circulating angiogenic cells in glioblastoma: Toward defining crucial functional differences in CAC-induced neoplastic versus reactive neovascularization'. Together they form a unique fingerprint.

Cite this