Increased levels of circulating endothelial progenitor cells and circulating endothelial nitric oxide synthase in patients with gliomas.
OBJECTIVE
Gliomas are among the highest vascularized tumors. We hypothesized that patients with gliomas have increased levels of circulating endothelial progenitor cells (EPCs) and circulating endothelial nitric oxide synthase (eNOS).


METHODS
The fraction of EPCs was quantified by fluorescence-activated cell sorter analysis using anti-CD34, -CD133 and -KDR (kinase insert domain receptor) monoclonal antibodies in unselected peripheral blood samples of 32 patients with gliomas. Control groups included 47 patients with other central nervous system tumors or diseases, 10 patients with recent ischemic strokes, and 19 healthy blood donors. The circulating eNOS concentration of plasma was measured by a colorimetric assay in the same samples. In addition, CD34(+)CD105(+) KDR(+) and CD34(+)CD146(+)KDR(-) cell fractions were measured.


RESULTS
The percentage of CD34(+)CD133(+)KDR(+) EPCs in the blood of glioma patients is significantly greater than that in the blood of patients with other central nervous system tumors or diseases (p = 0.003), stroke patients (p = 0.005), or healthy donors (p = 0.013). The plasma eNOS concentration is also significantly greater in glioma patients compared with each of the control groups (p < 0.001 for all groupwise comparisons). No significant differences in the levels of the EPCs or eNOS between any of the control groups were demonstrated. In the glioma patients, the level of eNOS correlated with the fraction of CD34(+)CD105(+)KDR(+) cells (r = 0.748; p = 0.008).


CONCLUSIONS
The data are suggestive of increased mobilization of EPCs contributing to neoplastic vasculogenesis in glioma. The increased levels of EPCs and eNOS in the peripheral blood of glioma patients trigger further investigations as to their value as independent parameters for use in clinical practice.
Zheng
Ping-Pin
PP
Department of Pathology, Erasmus Medical Center, Dr. Molewaterplein 50, 3000 DR Rotterdam, the Netherlands.
Hop
Wim C
WC
Luider
Theodorus M
TM
Sillevis Smitt
Peter A E
PA
Kros
Johan M
JM
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D042783:Endothelial Cells / Q000473:pathology*; D005260:Female; D005910:Glioma / Q000145:classification / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000097:blood*; D018709:Statistics, Nonparametric; D013234:Stem Cells / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D015703:Antigens, CD; D052250:Nitric Oxide Synthase Type III; D040301:Vascular Endothelial Growth Factor Receptor-2