Inhibition of the apelin/apelin receptor axis decreases cholangiocarcinoma growth

Chad Hall, Laurent Ehrlich, Julie Venter, April O'Brien, Tori White, Tianhao Zhou, Tien Dang, Fanyin Meng, Pietro Invernizzi, Francesca Bernuzzi, Gianfranco Alpini, Terry Lairmore, Shannon Glaser

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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 μg/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.

Original languageEnglish (US)
Pages (from-to)179-188
Number of pages10
JournalCancer Letters
Volume386
DOIs
StatePublished - Feb 1 2017
Externally publishedYes

Keywords

  • Apelin
  • Apelin receptor
  • Biliary epithelium
  • Cholangiocarcinoma
  • Proliferation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Hall, C., Ehrlich, L., Venter, J., O'Brien, A., White, T., Zhou, T., Dang, T., Meng, F., Invernizzi, P., Bernuzzi, F., Alpini, G., Lairmore, T., & Glaser, S. (2017). Inhibition of the apelin/apelin receptor axis decreases cholangiocarcinoma growth. Cancer Letters, 386, 179-188. https://doi.org/10.1016/j.canlet.2016.11.025