Apelin inhibition prevents resistance and metastasis associated with anti‐angiogenic therapy Number of metastatic lung foci in untreated (control) and.

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Apelin inhibition prevents resistance and metastasis associated with anti‐angiogenic therapy Number of metastatic lung foci in untreated (control) and sunitinib‐treated (60 mg/kg, three times a week from tumor initiation) NeuT;Apln+/+ or NeuT;Apln−/− mice, assessed 6 weeks after mammary tumors were size‐matched. Data of individual lung sections and means (black bars) are shown. Right panels show representative H&E images, where black arrows and insets indicate metastatic foci. Scale bars = 1,000 μm (large panels) and 50 μm (insets). *P < 0.05, **P < 0.01; ***P < 0.001; Kruskal–Wallis test; n = 3 mice per cohort and three sections per lung were analyzed. Kaplan–Meier survival plot for distant metastasis‐free survival from the KM‐plotter database (Győrffy et al, ) for high and low Apelin (APLN)‐expressing groups in human breast cancer. Patients were split by the median. Affymetrix Apelin ID 222856_at. Kaplan–Meier plot for progression‐free survival stratifying RCC patients with high and low APELIN serum levels 3–5 months after the start date of sunitinib treatment. *P = 0.0367; log‐rank test. Kaplan–Meier plots for progression‐free survival in RCC patients stratified into groups of high or low levels of APELIN and VEGF. Cutoff levels were set by the median. Serum was analyzed 3–5 months after the start date of sunitinib treatment. *P < 0.05, **P < 0.01; log‐rank test. Source data are available online for this figure. IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON PERMISSIONS@WILEY.COM OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSIONS' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER. EMBO Mol Med, First published: 24 June 2019, DOI: (10.15252/emmm.201809266)