Journal
CANCER LETTERS
Volume 386, Issue -, Pages 179-188Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.11.025
Keywords
Apelin; Apelin receptor; Cholangiocarcinoma; Biliary epithelium; Proliferation
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Funding
- Dr. Nicholas C. Hightower Centennial Chair of Gastroenterology from Scott White [5I01BX000574, 5I01BX002192]
- NIH [DK58411, DK07698, DK062975]
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Purpose: Cholangiocarcinoma (CCA) is a malignancy of the biliary epithelium that is associated with low five-year survival. The apelin receptor (APLNR), which is activated by the apelin peptide, has not been studied in CCA. The purpose of this study is to determine if inhibition of the apelin/APLNR axis can inhibit CCA growth. Methods: Immunohistochemistry, rtPCR, immunofluorescence, flow cytometry, and ELISA was used to measure APLNR expression in human CCA cells and tissues. Mz-ChA-1 cells were treated with increasing concentrations of apelin and ML221, an APLNR antagonist. Expression of proliferative and angiogenic genes were measured via rtPCR. In vivo, Mz-ChA-1 cells were injected into the flanks of nu/nu mice, which were treated with ML221 (150 mu g/kg) via tail vein injection. Results: Expression of the apelin/APLNR axis was increased in CCA. In vitro, CCA proliferation and angiogenesis was inhibited by ML221 treatment ML221 treatment significantly decreased tumor growth in nu/nu mice. Conclusion: The apelin/APLNR axis regulates CCA proliferation and angiogenesis. Inhibition of the apelin/APLNR axis decreases tumor growth in our xenograft model. Targeting APLNR signaling has the potential to serve as a novel, tumor directed therapy for CCA. (C) 2016 Published by Elsevier Ireland Ltd.
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