TY - JOUR
T1 - VEGFR2 expressing circulating (progenitor) cell populations in volunteers and cancer patients
AU - Vroling, Laura
AU - Yuana, Yuana
AU - Schuurhuis, Gerrit Jan
AU - van Hinsbergh, Victor W.M.
AU - Gundy, Chad
AU - de Haas, Richard
AU - van Cruijsen, Hester
AU - Boven, Epie
AU - Hoekman, Klaas
AU - Broxterman, Henk J.
PY - 2007/8/1
Y1 - 2007/8/1
N2 - Circulating cells of several lineages are thought to participate in angiogenesis and tumor growth. Experimental studies in tumor-bearing mice have pointed to the potential importance of VEGF-responding circulating (endothelial) progenitor cells in tumor growth.We have studied circulating CID31- and/or CD34-positive cell populations with a low to moderate VEGFR2 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 CD45neg/CD34bright/VEGFR2+ cells amounted to 12 and 64 cells/ml (P<0.0001), respectively, and 246/ml and 578/ml VEGFR2+/CD45bright (/CD14+) monocytic cells were present in controls and cancer patients, respectively (P=0.0 17). A third population of CD45dim/CD34bright/VEGFR2low cells amounted to 25 and 30 cells/ml (P=0.38). Unexpectedly, a population of mainly anucleated CD45low/CD31bright/CD41bright cells was present in numbers of 9,076 and 16,697/ml (P=0.04) in volunteers and cancer patients, which contained a VEGFR2low (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.
AB - Circulating cells of several lineages are thought to participate in angiogenesis and tumor growth. Experimental studies in tumor-bearing mice have pointed to the potential importance of VEGF-responding circulating (endothelial) progenitor cells in tumor growth.We have studied circulating CID31- and/or CD34-positive cell populations with a low to moderate VEGFR2 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 CD45neg/CD34bright/VEGFR2+ cells amounted to 12 and 64 cells/ml (P<0.0001), respectively, and 246/ml and 578/ml VEGFR2+/CD45bright (/CD14+) monocytic cells were present in controls and cancer patients, respectively (P=0.0 17). A third population of CD45dim/CD34bright/VEGFR2low cells amounted to 25 and 30 cells/ml (P=0.38). Unexpectedly, a population of mainly anucleated CD45low/CD31bright/CD41bright cells was present in numbers of 9,076 and 16,697/ml (P=0.04) in volunteers and cancer patients, which contained a VEGFR2low (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.
KW - CD31
KW - Cancer
KW - Circulating endothelial cells
KW - Circulating progenitor cells
KW - KDR
KW - Large platelets
KW - Peripheral blood
KW - VEGFR2
UR - http://www.scopus.com/inward/record.url?scp=34547865008&partnerID=8YFLogxK
U2 - https://doi.org/10.1160/TH07-03-0225
DO - https://doi.org/10.1160/TH07-03-0225
M3 - Article
C2 - 17721629
SN - 0340-6245
VL - 98
SP - 440
EP - 450
JO - Thrombosis and haemostasis
JF - Thrombosis and haemostasis
IS - 2
ER -