Article

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

Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, Amsterdam, The Netherlands.
Angiogenesis (Impact Factor: 4.41). 03/2009; 12(1):69-79. DOI: 10.1007/s10456-009-9133-9
Source: PubMed

ABSTRACT 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.

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    • "Their clinical significance is still under investigation. Recent studies have observed increased levels of CECs in RCC patients treated with sunitinib, likely caused by the drug targeting of immature tumor vessels [11]. EPCs express CD133, CD34, and VEGFR-2 [12]. "
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    • "The cutoff value for CD133 positivity in HPCs was determined based on isotype control and was adjusted for every individual sample. CECs are CD34 bright , which are almost uniformly positive for VEGFR2, but lack both markers CD45 and CD133 as previously defined (Vroling et al, 2007, 2009) (Figure 1). "
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