Polychromatic flow cytometry identifies novel subsets of circulating cells with angiogenic potential in pediatric solid tumors

摘要

Pediatric solid tumors depend upon angiogenesis for their growth and metastases. A new polychromatic flow cytometry (PFC) protocol has revealed circulating cells of hematopoietic and endothelial lineages from the peripheral blood (PB) of healthy individuals, and has defined the different cell types involved in the growth of tumor vasculature that are critical in angiogenesis. Methods: PB was collected from both healthy children and children with different malignant solid tumors and the mononuclear cells (MNCs) were subsequently isolated. PFC was applied and the MNCs were evaluated for proangiogenic and nonangiogenic circulating progenitor cells (CPCs), endothelial colony forming cells (ECFCs), and mature endothelial cells using the markers CD45, CD31, AC133, CD34, CD14, CD235a, CD41a, and a viability marker. Results: ECFCs and CPCs were significantly elevated in patients at day 21 compared to controls. The ratio of proangiogenic to nonangiogenic CPCs was significantly elevated compared to controls at baseline and returned to healthy baseline levels following treatment. Conclusions: We describe the successful identification of these hematopoietic and endothelial progenitor cells in both healthy children and children with solid tumors. In addition, this is a potential discovery of novel predictive biomarkers for future clinical trials.