title: Increased numbers of small circulating endothelial cells in renal cell cancer patients treated with sunitinib.
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.
authors.affiliation: Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, Amsterdam, The Netherlands. l.vroling@vumc.nl
authors.forename: Laura
authors.initials: L
authors.lastname: Vroling
authors.forename: Astrid A M
authors.initials: AA
authors.lastname: van der Veldt
authors.forename: Richard R
authors.initials: RR
authors.lastname: de Haas
authors.forename: John B A G
authors.initials: JB
authors.lastname: Haanen
authors.forename: Gerrit Jan
authors.initials: GJ
authors.lastname: Schuurhuis
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Kuik
authors.forename: Hester
authors.initials: H
authors.lastname: van Cruijsen
authors.forename: Henk M W
authors.initials: HM
authors.lastname: Verheul
authors.forename: Alfons J M
authors.initials: AJ
authors.lastname: van den Eertwegh
authors.forename: Klaas
authors.initials: K
authors.lastname: Hoekman
authors.forename: Epie
authors.initials: E
authors.lastname: Boven
authors.forename: Victor W M
authors.initials: VW
authors.lastname: van Hinsbergh
authors.forename: Henk J
authors.initials: HJ
authors.lastname: Broxterman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D001772:Blood Cell Count; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy*; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D004921:Erythropoietin / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D000077210:Sunitinib; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000097:blood
chemical_list: D018952:Antigens, CD34; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; D011758:Pyrroles; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; D000077210:Sunitinib