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

Molecular Oncology - Tập 9 - Trang 270-281 - 2015
Luke H. Hoeppner1, Ying Wang1, Anil Sharma1, Naureen Javeed1, Virginia P. Van Keulen2, Enfeng Wang1, Ping Yang3,4, Anja C. Roden5, Tobias Peikert2,3, Julian R. Molina5,6, Debabrata Mukhopadhyay1
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
4Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
5Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
6Department of Medicine, Division of Medical Oncology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA

Tóm tắt

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.

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Molecular Oncology

Tập 9

270-281

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