Dopamine D2 receptor agonists inhibit lung cancer progression by reducing angiogenesis and tumor infiltrating myeloid derived suppressor cells. Issue 1 (30th August 2014)

• Record Type: Journal Article
• Authors: Hoeppner, Luke H.; Wang, Ying; Sharma, Anil; Javeed, Naureen; Van Keulen, Virginia P.; Wang, Enfeng; Yang, Ping; Roden, Anja C.; Peikert, Tobias; Molina, Julian R.; Mukhopadhyay, Debabrata
• Is Part Of: Molecular oncology. Volume 9:Issue 1(2015:Jan.)
• Page Start: 270
• Page End: 281
• Publication Date: 2014-08-30
• Subjects: Dopamine -- Lung cancer -- VEGF -- Cabergoline -- Angiogenesis -- Dopamine D2 receptor agonists; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1016/j.molonc.2014.08.008
• Languages: English
• ISSNs: 1574-7891

Abstract

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. Highlights: D2R agonists inhibit lung tumor progression in murine models of lung cancer. D2R agonists reduce tumor angiogenesis and myeloid derived suppressor cells. Endothelial D2R correlates with patients' lung tumor grade and smoking history. Cabergoline shows promise as a targeted therapy and warrants clinical investigation.