Journal article
Biologic Effects of Dopamine on Tumor Vasculature in Ovarian Carcinoma
Neoplasia (New York, N.Y.), Vol.15(5), pp.502-510
05/2013
DOI: 10.1593/neo.121412
PMID: 23633922
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.
Details
- Title: Subtitle
- Biologic Effects of Dopamine on Tumor Vasculature in Ovarian Carcinoma
- Creators
- Myrthala Moreno-Smith - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TXSun Joo Lee - Department of Obstetrics and Gynecology, Konkuk University Hospital, Konkuk University School of Medicine, Seoul, South KoreaChunhua Lu - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TXArchana S Nagaraja - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TXGuangan He - Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TXRajesha Rupaimoole - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TXHee Dong Han - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TXNicholas B Jennings - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TXJu-Won Roh - Department of Obstetrics and Gynecology, Dongguk University Ilsan Hospital, Goyang, South KoreaMasato Nishimura - Department of Obstetrics and Gynecology, The University of Tokushima Graduate School, Tokushima, JapanYu Kang - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TXJulie K Allen - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TXGuillermo N Armaiz - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TXKoji Matsuo - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TXMian M K Shahzad - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TXJustin Bottsford-Miller - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TXRobert R Langley - Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TXSteve W Cole - Department of Medicine, Division of Hematology and Oncology, University of California, Los Angeles School of Medicine, Los Angeles, CASusan K Lutgendorf - Departments of Psychology and Gynecology and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IAZahid H Siddik - Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TXAnil K Sood - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
- Resource Type
- Journal article
- Publication Details
- Neoplasia (New York, N.Y.), Vol.15(5), pp.502-510
- DOI
- 10.1593/neo.121412
- PMID
- 23633922
- NLM abbreviation
- Neoplasia
- ISSN
- 1476-5586
- eISSN
- 1476-5586
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 05/2013
- Academic Unit
- Psychological and Brain Sciences; Iowa Neuroscience Institute; Obstetrics and Gynecology; Urology
- Record Identifier
- 9984065885102771
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