Ovarian cancer has the highest mortality rate among gynecologic malignancies. Due to poor survival of women with epithelial ovarian cancer, identification of factors responsible for accelerated cancer growth may have significance for clinical outcomes. Stress can elicit alterations of immunological, neurochemical, and endocrinological functions. While most of the research dealing with stress and accelerated tumor growth has focused on suppressed immunity, during our initial funding period we have uncovered new mechanisms by which chronic stress affects the tumor microenvironment. We established that sympathetic nervous system (SNS) activation in response to chronic stress resulted in increased production of pro- angiogenic factors by tumor cells. This increase was responsible for promoting tumor vascularity and perfusion. These effects were mediated by the 22-adrenergic receptors (ADRB2) on tumor cells and were blocked by beta-antagonists. However, there is third member of the catecholamine family, dopamine, which is known to have anti-angiogenic effects, but it is decreased in response to chronic stress. This project is designed to characterize dopamine levels in ovarian cancer using chronic stress models as well as human ovarian cancers. Furthermore, we will determine the expression levels of dopamine receptors in both ovarian cancer and endothelial cells. We will also analyze the biological effects of dopamine replacement using our well-characterized orthotopic model of ovarian carcinoma. Findings of this study could lead to identification of novel mechanisms underlying accelerated ovarian cancer growth and therefore may lead to new therapeutic approaches.

Public Health Relevance

Chronic stress can affect many aspects of health and is suspected to play a role in promoting cancer growth, but the underlying mechanisms are not well understood. Our studies are designed to provide a mechanistic understanding of how chronic stress promotes cancer growth and to devise strategies for overcoming these effects. The results from this work could be important for designing new methods of treatment of cancer patients.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BBBP-C (02))
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Mc Donald, Paige A
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University of Texas MD Anderson Cancer Center
Other Health Professions
Other Domestic Higher Education
United States
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Bottsford-Miller, Justin; Choi, Hyun-Jin; Dalton, Heather J et al. (2015) Differential platelet levels affect response to taxane-based therapy in ovarian cancer. Clin Cancer Res 21:602-10
Wen, Yunfei; Graybill, Whitney S; Previs, Rebecca A et al. (2015) Immunotherapy targeting folate receptor induces cell death associated with autophagy in ovarian cancer. Clin Cancer Res 21:448-59
Previs, Rebecca A; Coleman, Robert L; Harris, Adrian L et al. (2015) Molecular pathways: translational and therapeutic implications of the Notch signaling pathway in cancer. Clin Cancer Res 21:955-61
Stone, Rebecca L; Baggerly, Keith A; Armaiz-Pena, Guillermo N et al. (2014) Focal adhesion kinase: an alternative focus for anti-angiogenesis therapy in ovarian cancer. Cancer Biol Ther 15:919-29
Roh, Ju-Won; Huang, Jie; Hu, Wei et al. (2014) Biologic effects of platelet-derived growth factor receptor ? blockade in uterine cancer. Clin Cancer Res 20:2740-50
Gharpure, Kshipra M; Chu, Kevin S; Bowerman, Charles J et al. (2014) Metronomic docetaxel in PRINT nanoparticles and EZH2 silencing have synergistic antitumor effect in ovarian cancer. Mol Cancer Ther 13:1750-7
Wen, Yunfei; Zand, Behrouz; Ozpolat, Bulent et al. (2014) Antagonism of tumoral prolactin receptor promotes autophagy-related cell death. Cell Rep 7:488-500
Rupaimoole, Rajesha; Wu, Sherry Y; Pradeep, Sunila et al. (2014) Hypoxia-mediated downregulation of miRNA biogenesis promotes tumour progression. Nat Commun 5:5202
Reusser, Nicole M; Dalton, Heather J; Pradeep, Sunila et al. (2014) Clodronate inhibits tumor angiogenesis in mouse models of ovarian cancer. Cancer Biol Ther 15:1061-7
Cho, Min Soon; Vasquez, Hernan G; Rupaimoole, Rajesha et al. (2014) Autocrine effects of tumor-derived complement. Cell Rep 6:1085-95

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