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

32 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

Funding Information:
The authors thank the Mayo Clinic pathology research core facility for their assistance with this research. This work was partly supported by CA78383 , CA150190 , and HL70567 (to D. Mukhopadhyay). L.H. Hoeppner is a fellow of NCI-T32 CA148073 and 13POST14510025 from the American Heart Association . Y. Wang is supported by 14POST20390029 from the American Heart Association.

Publisher Copyright:
© 2014 Federation of European Biochemical Societies.

Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.

Keywords

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

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