title: Dopamine D2 receptor agonists inhibit lung cancer progression by reducing angiogenesis and tumor infiltrating myeloid derived suppressor cells.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Luke H
authors.initials: LH
authors.lastname: Hoeppner
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Naureen
authors.initials: N
authors.lastname: Javeed
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Virginia P
authors.initials: VP
authors.lastname: Van Keulen
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Enfeng
authors.initials: E
authors.lastname: Wang
authors.affiliation: Department 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.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Anja C
authors.initials: AC
authors.lastname: Roden
authors.affiliation: Department 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.
authors.forename: Tobias
authors.initials: T
authors.lastname: Peikert
authors.affiliation: Department 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.
authors.forename: Julian R
authors.initials: JR
authors.lastname: Molina
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. Electronic address: mukhopadhyay.debabrata@mayo.edu.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Mukhopadhyay
mesh_terms: D000818:Animals; D065127:Dopamine D2 Receptor Antagonists / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D022423:Myeloid Cells / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2
keywords: Angiogenesis; Cabergoline; Dopamine; Dopamine D2 receptor agonists; Lung cancer; VEGF