Psychosocial stress can elicit complex effects on the immune and other systems in cancer patients through mechanisms including the sympathetic nervous system (SNS), the hypothalamic-pituitary-adrenal (HPA) axis, and by other hormones and peptides. These catecholamine changes in the tumor microenvironment trigger a cascade of signaling events that create a highly permissive environment for tumor growth and metastasis. We have demonstrated that elevation of SNS mediators (e.g., catecholamines) in the tumor microenvironment can increase angiogenesis and block anoikis. However, the mechanisms by which catecholamines are delivered to the tumor microenvironment are not well understood. On the basis of our preliminary data, we hypothesize that there is increased tumor innervation in response to chronic stress, which promotes epithelial-to-mesenchymal transition (EMT) and metastasis. In this renewal application, we will examine the mechanisms by which chronic stress contributes to increased innervation and, and examine the resultant biological consequences using well-characterized orthotropic mouse models of ovarian cancer. We will also examine relationships between psychosocial stress factors and nerve density in tumors from patients. Findings from this proposal could lead to identification of novel mechanisms underlying accelerated ovarian cancer growth and therefore may lead to new preventive and therapeutic strategies.

Public Health Relevance

This Renewal R01 application focuses on investigating the mechanisms by which increased tumor innervation in response to chronic stress promotes epithelial-to-mesenchymal transition (EMT) and metastasis in ovarian cancer. Findings from this proposal could lead to identification of novel mechanisms underlying accelerated ovarian cancer growth and therefore may lead to new preventive and therapeutic strategies.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Green, Paige A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas MD Anderson Cancer Center
Obstetrics & Gynecology
Other Domestic Higher Education
United States
Zip Code
Nagaraja, Archana S; Dood, Robert L; Armaiz-Pena, Guillermo et al. (2017) Adrenergic-mediated increases in INHBA drive CAF phenotype and collagens. JCI Insight 2:
Cuneo, Michaela G; Schrepf, Andrew; Slavich, George M et al. (2017) Diurnal cortisol rhythms, fatigue and psychosocial factors in five-year survivors of ovarian cancer. Psychoneuroendocrinology 84:139-142
Dalton, Heather J; Pradeep, Sunila; McGuire, Michael et al. (2017) Macrophages Facilitate Resistance to Anti-VEGF Therapy by Altered VEGFR Expression. Clin Cancer Res 23:7034-7046
Westin, Shannon N; Coleman, Robert L (2017) Individualized Medicine in Ovarian Cancer: Are We There Yet? Gynecol Oncol 144:229-231
Previs, Rebecca A; Armaiz-Pena, Guillermo N; Ivan, Cristina et al. (2017) Role of YAP1 as a Marker of Sensitivity to Dual AKT and P70S6K Inhibition in Ovarian and Uterine Malignancies. J Natl Cancer Inst 109:
Lutgendorf, Susan K; Thaker, Premal H; Arevalo, Jesusa M et al. (2017) Biobehavioral modulation of the exosome transcriptome in ovarian carcinoma. Cancer :
Lutgendorf, Susan K; Shinn, Eileen; Carter, Jeanne et al. (2017) Quality of life among long-term survivors of advanced stage ovarian cancer: A cross-sectional approach. Gynecol Oncol 146:101-108
Gangwar, Ruchika; Meena, Avtar S; Shukla, Pradeep K et al. (2017) Calcium-mediated oxidative stress: a common mechanism in tight junction disruption by different types of cellular stress. Biochem J 474:731-749
Haemmerle, Monika; Taylor, Morgan L; Gutschner, Tony et al. (2017) Platelets reduce anoikis and promote metastasis by activating YAP1 signaling. Nat Commun 8:310
Noh, Kyunghee; Mangala, Lingegowda S; Han, Hee-Dong et al. (2017) Differential Effects of EGFL6 on Tumor versus Wound Angiogenesis. Cell Rep 21:2785-2795

Showing the most recent 10 out of 156 publications