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

Mol Oncol. 2015 Jan;9(1):270-81. doi: 10.1016/j.molonc.2014.08.008. Epub 2014 Aug 30.

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.

Keywords: Angiogenesis; Cabergoline; Dopamine; Dopamine D2 receptor agonists; Lung cancer; VEGF.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopamine D2 Receptor Antagonists / pharmacology*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Humans
  • Lung Neoplasms* / blood supply
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Mice
  • Myeloid Cells* / metabolism
  • Myeloid Cells* / pathology
  • Neovascularization, Pathologic* / drug therapy
  • Neovascularization, Pathologic* / metabolism
  • Neovascularization, Pathologic* / pathology
  • Receptors, Dopamine D2 / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • Dopamine D2 Receptor Antagonists
  • Receptors, Dopamine D2