Mobilization of circulating vascular progenitors in cancer patients receiving external beam radiation in response to tissue injury.
OBJECTIVE
Endothelial-like vascular progenitor cells (VPCs) are associated with the repair of ischemic tissue injury in several clinical settings. Because the endothelium is a principal target of radiation injury, VPCs may be important in limiting toxicity associated with radiotherapy (RT) in patients with cancer.


METHODS
We studied 30 patients undergoing RT for skin cancer (n = 5), head-and-neck cancer (n = 15), and prostate cancer (n = 10) prospectively, representing a wide range of irradiated mucosal volumes. Vascular progenitor cell levels were enumerated from peripheral blood at baseline, midway through RT, at the end of treatment, and 4 weeks after radiation. Acute toxicity was graded at each time point by use of the National Cancer Institute's Common Toxicity Criteria, version 3.0.


RESULTS
Significant increases in the proportion of CD34(+)/CD133(+) VPCs were observed after completion of RT, from 0.012% at baseline to 0.048% (p = 0.029), and the increase in this subpopulation was most marked in patients with Grade 2 peak toxicity or greater after RT (p = 0.034). Similarly, CD34(+)/vascular endothelial growth factor receptor 2-positive VPCs were increased after the completion of radiation therapy in comparison to baseline (from 0.014% to 0.027%, p = 0.043), and there was a trend toward greater mobilization in patients with more significant toxicity (p = 0.08). The mobilization of CD34(+) hematopoietic stem cells did not increase after treatment (p = 0.58), and there was no relationship with toxicity.


CONCLUSIONS
We suggest that VPCs may play an important role in reducing radiation-induced tissue damage. Interventions that increase baseline VPC levels or enhance their mobilization and recruitment in response to RT may prove useful in facilitating more rapid and complete tissue healing.
Allan
David S
DS
Ottawa Health Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada. daallan@ohri.ca
Morgan
Scott C
SC
Birch
Paul E
PE
Yang
Lin
L
Halpenny
Michael J
MJ
Gunanayagam
Angelo
A
Li
Yuhua
Y
Eapen
Libni
L
D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D002452:Cell Count / Q000379:methods; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000502:physiology* / Q000528:radiation effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000528:radiation effects*; D005260:Female; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000532:radiotherapy; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000528:radiation effects; D008297:Male; D009092:Mucous Membrane / Q000166:cytology / Q000528:radiation effects; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000532:radiotherapy; D011832:Radiation Injuries / Q000517:prevention & control; D011879:Radiotherapy Dosage; D012878:Skin Neoplasms / Q000532:radiotherapy; D013234:Stem Cells / Q000502:physiology* / Q000528:radiation effects; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis
D018952:Antigens, CD34; D040301:Vascular Endothelial Growth Factor Receptor-2