title: Biologic effects of dopamine on tumor vasculature in ovarian carcinoma.
abstract: Chronic sympathetic nervous system activation results in increased angiogenesis and tumor growth in orthotopic mouse models of ovarian carcinoma. However, the mechanistic effects of such activation on the tumor vasculature are not well understood. Dopamine (DA), an inhibitory catecholamine, regulates the functions of normal and abnormal blood vessels. Here, we examined whether DA, an inhibitory catecholamine, could block the effects of chronic stress on tumor vasculature and tumor growth. Exogenous administration of DA not only decreased tumor microvessel density but also increased pericyte coverage of tumor vessels following daily restraint stress in mice. Daily restraint stress resulted in significantly increased tumor growth in the SKOV3ip1 and HeyA8 ovarian cancer models. DA treatment blocked stress-mediated increases in tumor growth and increased pericyte coverage of tumor endothelial cells. Whereas the antiangiogenic effect of DA is mediated by dopamine receptor 2 (DR2), our data indicate that DA, through DR1, stimulates vessel stabilization by increasing pericyte recruitment to tumor endothelial cells. DA significantly stimulated migration of mouse 10T1/2 pericyte-like cells in vitro and increased cyclic adenosine mono-phosphate (cAMP) levels in these cells. Moreover, DA or the DR1 agonist SKF 82958 increased platinum concentration in SKOV3ip1 tumor xenografts following cisplatin administration. In conclusion, DA stabilizes tumor blood vessels through activation of pericyte cAMP-protein kinase A signaling pathway by DR1. These findings could have implications for blocking the stimulatory effects of chronic stress on tumor growth.
authors: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Myrthala
authors: M
authors: Moreno-Smith
authors: Sun Joo
authors: SJ
authors: Lee
authors: Chunhua
authors: C
authors: Lu
authors: Archana S
authors: AS
authors: Nagaraja
authors: Guangan
authors: G
authors: He
authors: Rajesha
authors: R
authors: Rupaimoole
authors: Hee Dong
authors: HD
authors: Han
authors: Nicholas B
authors: NB
authors: Jennings
authors: Ju-Won
authors: JW
authors: Roh
authors: Masato
authors: M
authors: Nishimura
authors: Yu
authors: Y
authors: Kang
authors: Julie K
authors: JK
authors: Allen
authors: Guillermo N
authors: GN
authors: Armaiz
authors: Koji
authors: K
authors: Matsuo
authors: Mian M K
authors: MM
authors: Shahzad
authors: Justin
authors: J
authors: Bottsford-Miller
authors: Robert R
authors: RR
authors: Langley
authors: Steve W
authors: SW
authors: Cole
authors: Susan K
authors: SK
authors: Lutgendorf
authors: Zahid H
authors: ZH
authors: Siddik
authors: Anil K
authors: AK
authors: Sood
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D002395:Catecholamines / Q000494:pharmacology / Q000502:physiology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000493:pharmacokinetics / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology* / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology; D004357:Drug Synergism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D020286:Pericytes / Q000187:drug effects / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D015290:Second Messenger Systems; D013312:Stress, Physiological; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001552:Benzazepines; D002395:Catecholamines; D015259:Dopamine Agents; D011943:Receptors, Adrenergic, beta; D011954:Receptors, Dopamine; C071262:SK&F 82958; D002945:Cisplatin; D004298:Dopamine
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