Increased numbers of small circulating endothelial cells in renal cell cancer patients treated with sunitinib

• Published in: Angiogenesis (London) Vol. 12; no. 1; pp. 69 - 79
• Main Authors: Vroling, Laura, van der Veldt, Astrid A. M., de Haas, Richard R., Haanen, John B. A. G., Schuurhuis, Gerrit Jan, Kuik, Dirk J., van Cruijsen, Hester, Verheul, Henk M. W., van den Eertwegh, Alfons J. M., Hoekman, Klaas, Boven, Epie, van Hinsbergh, Victor W. M., Broxterman, Henk J.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.03.2009; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, CD34 - metabolism; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Biomarkers, Tumor - blood; Biomedical and Life Sciences; Biomedicine; Blood and lymphatic vessels; Blood Cell Count; Blood vessels and receptors; Cancer Research; Carcinoma, Renal Cell - blood; Carcinoma, Renal Cell - drug therapy; Cardiology; Cardiology. Vascular system; Cell Biology; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Endothelial Cells - cytology; Endothelial Cells - drug effects; Erythropoietin - blood; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Hematopoietic Stem Cells - drug effects; Humans; Indoles - pharmacology; Indoles - therapeutic use; Kidney Neoplasms - blood; Kidney Neoplasms - drug therapy; Kinetics; Male; Medical sciences; Middle Aged; Oncology; Ophthalmology; Original Paper; Pyrroles - pharmacology; Pyrroles - therapeutic use; Treatment Outcome; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Vascular Endothelial Growth Factor A - blood; Vertebrates: cardiovascular system; Circulating endothelial (progenitor) cells; Renal cell cancer patients; Sunitinib; Erythropoietin; VEGF; Antineoplastic agent; Endothelial cell; Cardiovascular disease; Antiangiogenic agent; Protein-tyrosine kinase; Tumor cell; Kidney disease; Human; Urinary system disease; Enzyme; Tyrosine kinase inhibitor; Transferases; Enzyme inhibitor; Malignant tumor; Treatment; Polypeptide; Kidney cancer; Multikinase inhibitor; Cancer; Progenitor cell
• ISSN: 0969-6970; 1573-7209
• DOI: 10.1007/s10456-009-9133-9

Mature circulating endothelial cell (CEC) as well as endothelial progenitor populations may reflect the activity of anti-angiogenic agents on tumor neovasculature or even constitute a target for anti-angiogenic therapy. We investigated the behavior of CECs in parallel with hematopoietic progenitor cells (HPCs) in the blood of renal cell cancer patients during sunitinib treatment. We analyzed the kinetics of a specific population of small VEGFR2-expressing CECs (CD45 neg /CD34 bright ), HPCs (CD45 dim /CD34 bright ), and monocytes in the blood of 24 renal cell cancer (RCC) patients receiving 50 mg/day of the multitargeted VEGF inhibitor sunitinib, on a 4-week-on/2-week-off schedule. Blood was taken before treatment (C1D1), on C1D14, C1D28, and on C2D1 before the start of cycle 2. Also plasma VEGF and erythropoietin (EPO) were determined. Remarkably, while CD34 bright HPCs and monocytes decreased during treatment, CD34 bright CECs increased from 69 cells/ml (C1D1) to 180 cells/ml (C1D14; P  = 0.001) and remained high on C1D28. All cell populations recovered to near pre-treatment levels on C2D1. Plasma VEGF and EPO levels were increased on C1D14 and partly normalized to pre-treatment levels on C2D1. In conclusion, opposite kinetics of two circulating CD34 bright cell populations, HPCs and small CECs, were observed in sunitinib-treated RCC patients. The increase in CECs is likely caused by sunitinib targeting of immature tumor vessels.