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

Mol Oncol. 2014 Aug 30. pii: S1574-7891(14)00203-8. doi: 10.1016/j.molonc.2014.08.008. [Epub ahead of print]

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

Hoeppner LH1, Wang Y1, Sharma A1, Javeed N1, Van Keulen VP2, Wang E1, Yang P3, Roden AC4, Peikert T5, Molina JR6, Mukhopadhyay D7.

Author information

• 1Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
• 2Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
• 3Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
• 4Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
• 5Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
• 6Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; Department of Medicine, Division of Medical Oncology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
• 7Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. Electronic address: mukhopadhyay.debabrata@mayo.edu.

Abstract

We sought to determine whether Dopamine D2 Receptor (D2R) agonists inhibit lung tumor progression and identify subpopulations of lung cancerpatients 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.