VEGFR2 expressing circulating (progenitor) cell populations in volunteers and cancer patients

Laura Vroling; Yuana Yuana; Gerrit Jan Schuurhuis; Victor W. M. van Hinsbergh; Chad Gundy; Richard de Haas; Hester van Cruijsen; Epie Boven; Klaas Hoekman; Henk J. Broxterman

doi:10.1160/TH07-03-0225

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 98(02): 440-450
DOI: 10.1160/TH07-03-0225

Cellular Proteolysis and Oncology

Schattauer GmbH

VEGFR2 expressing circulating (progenitor) cell populations in volunteers and cancer patients

Authors

Laura Vroling

¹Departments of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
Yuana Yuana

¹Departments of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
Gerrit Jan Schuurhuis

²Departments of Hematology, VU University Medical Center, Amsterdam, The Netherlands
Victor W. M. van Hinsbergh

³Departments of Physiology, VU University Medical Center, Amsterdam, The Netherlands
Chad Gundy

⁴Departments of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
Richard de Haas

¹Departments of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
Hester van Cruijsen

¹Departments of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
Epie Boven

¹Departments of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
Klaas Hoekman

¹Departments of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
Henk J. Broxterman

¹Departments of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands

Abstract

Summary

Circulating cells of several lineages are thought to participate in angiogenesis and tumor growth. Experimental studies in tumorbearing mice have pointed to the potential importance of VEGFresponding circulating (endothelial) progenitor cells in tumor growth.We have studied circulating CD31- and/or CD34-positive cell populations with a low to moderateVEGFR2 expression in human volunteers and cancer patients. We recognized four cell populations, which were further characterized by their content of major hematopoetic progenitor, monocytic, endothelial and platelet markers. After establishing the test-retest stability of the measurements in nine patients, we determined the frequencies of the various cell populations in a group of 20 volunteers and 14 cancer patients.Two populations were markedly increased in cancer patients. Small CD45^neg /CD34^bright/VEGFR2+ cells amounted to 12 and 64 cells/ml (P<0.0001), respectively, and 246/ml and 578/ml VEGFR2+/CD45^bright (/CD14+) monocytic cells were present in controls and cancer patients, respectively (P=0.017). A third population of CD45^dim/CD34^bright/ VEGFR2^low cells amounted to 25 and 30 cells/ml (P=0.38).Unexpectedly, a population of mainly anucleated CD45^low/CD31^bright/ CD41^bright cells was present in numbers of 9,076 and 16,697/ml (P=0.04) in volunteers and cancer patients, which contained a VEGFR2^low (compared to IgG isotype control) expressing population amounting to 1,142 and 1,642 cells/ml (P=0.12). This fourth population probably reflects large platelets. The role of the herein identified VEGFR2⁺ circulating cell populations deserve further investigation in cancer patients treated with VEGF(R)-targeted therapies. Quantification of such cell populations in the blood of tumor patients may be valuable to monitor the efficacy of anti-angiogenic treatment.

Keywords

Circulating progenitor cells - circulating endothelial cells - VEGFR2 - KDR - CD31 - peripheral blood - large platelets - cancer

Full Text

References

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