Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10914815 | Molecular Oncology | 2015 | 12 Pages |
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
EGFRDopamine D2 receptor agonistsMDSCsTKIALK1D2RHUVECROSAngiogenesisDopamineLung cancerNSCLCNon-small cell lung cancerHuman umbilical vein endothelial cellsMyeloid derived suppressor cellsVascular Endothelial Growth Factor (VEGF)Vascular endothelial growth factor ATyrosine kinase inhibitorsCabergolineReactive oxygen speciesdopamine D2 receptorEpidermal growth factor receptor
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Authors
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,