Dopamine D2 receptor agonists inhibit lung cancer progression by reducing angiogenesis and tumor infiltrating myeloid derived suppressor cells

Luke H. Hoeppner, Ying Wang, Anil Sharma, Naureen Javeed, Virginia P. Van Keulen, Enfeng Wang, Ping Yang, Anja C. Roden, Tobias Peikert, Julian R. Molina, Debabrata Mukhopadhyay

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

We sought to determine whether Dopamine D2 Receptor (D2R) agonists inhibit lung tumor progression and identify subpopulations of lung cancer patients that benefit most from D2R agonist therapy. We demonstrate D2R agonists abrogate lung tumor progression in syngeneic (LLC1) and human xenograft (A549) orthotopic murine models through inhibition of tumor angiogenesis and reduction of tumor infiltrating myeloid derived suppressor cells. Pathological examination of human lung cancer tissue revealed a positive correlation between endothelial D2R expression and tumor stage. Lung cancer patients with a smoking history exhibited greater levels of D2R in lung endothelium. Our results suggest D2R agonists may represent a promising individualized therapy for lung cancer patients with high levels of endothelial D2R expression and a smoking history.

Original languageEnglish (US)
Pages (from-to)270-281
Number of pages12
JournalMolecular Oncology
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2014 Federation of European Biochemical Societies.

Keywords

  • Angiogenesis
  • Cabergoline
  • Dopamine
  • Dopamine D2 receptor agonists
  • Lung cancer
  • VEGF

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