MP71-16 INTERMITENT HYPOXIA INCREASES TUMOR ANGIOGENESIS IN A MOUSE MODEL OF KIDNEY CANCER

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I1 Apr 2016MP71-16 INTERMITENT HYPOXIA INCREASES TUMOR ANGIOGENESIS IN A MOUSE MODEL OF KIDNEY CANCER Antoni Vilaseca, Mireia Musquera, Marta Torres, Noelia Campillo, Josep M Montserrat, Karim Touijer, Ramon Farre, Isaac Almendros, and Antonio Alcaraz Antoni VilasecaAntoni Vilaseca More articles by this author , Mireia MusqueraMireia Musquera More articles by this author , Marta TorresMarta Torres More articles by this author , Noelia CampilloNoelia Campillo More articles by this author , Josep M MontserratJosep M Montserrat More articles by this author , Karim TouijerKarim Touijer More articles by this author , Ramon FarreRamon Farre More articles by this author , Isaac AlmendrosIsaac Almendros More articles by this author , and Antonio AlcarazAntonio Alcaraz More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1462AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Intermittent hypoxia (IH), a characteristic feature of obstructive sleep apnea (OSA), has been recently associated with an increased cancer aggressiveness and mortality. Renal cell carcinoma is commonly linked to an increased expression of hypoxia-inducible genes promoting neovascularization, and can result in poorest prognosis. We aim to assess the role of IH on tumor angiogenesis as a marker of malignancy in a mouse model of renal cell carcinoma and to study in vitro the role of isolated tumor cells on promoting angiogenesis under IH. METHODS A subcutaneous kidney cancer was induced in 24 Balb/c mice by injecting 105 RENCA cells in the left flank. Twelve mice were subjected to IH (cycles of 20s at 5% O2 followed by 40s at 21% O2, 6h/day) from 15 days before injection until 21 days after injection, when they were sacrificed. A control group (n=12) was kept under normoxia for the same period of time. After sacrifice, tumors were excised and processed to evaluate the presence of endothelial progenitor cells (CD309+Gr1+) and endothelial cells (CD31+) by flow cytometry. Circulating vascular endothelial growth factor (VEGF) was quantified by ELISA. We also tested in vitro the hypothesis that isolated RENCA cells subjected to IH increase VEGF production. We seeded 5x104 RENCA cells/well in two 6-well plates. After 12 hours we kept for 24 hours each 6-well plate under normoxia and IH, respectively. Supernatant VEGF quantification was done by ELISA. RESULTS Percentage of vascular progenitor cells in tumoral tissue was increased under IH compared to normoxia (6,1 ± 0,76 vs 4,5±1,1; p=0,001). Similarly, the percentage of endothelial cells was also promoted by IH (4±0,8 vs 2,5±1; p=0,013). Plasma VEGF was significantly higher among the IH group (306±93 vs 204±45 pg/mL; p=0,001). Tumor growth was not affected by IH (0,7±0,6 vs 0,8±0,42 gr; p=0,08). In the in vitro experiments, VEGF in the supernatant after 24h of culture did not differ between IH and normoxia (719±63 vs 729±192 pg/mL; p=0,912). CONCLUSIONS In the animal model, IH increases the production of circulating VEGF and the mobilization of vascular progenitor cells, resulting in an increased vascularization of the tumor. In vitro, isolated tumor cells do not increase VEGF production under IH compared to normoxia. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e921-e922 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Antoni Vilaseca More articles by this author Mireia Musquera More articles by this author Marta Torres More articles by this author Noelia Campillo More articles by this author Josep M Montserrat More articles by this author Karim Touijer More articles by this author Ramon Farre More articles by this author Isaac Almendros More articles by this author Antonio Alcaraz More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...