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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA109298-13
Application #
9203616
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Green, Paige A
Project Start
2004-07-01
Project End
2019-01-31
Budget Start
2017-02-01
Budget End
2018-01-31
Support Year
13
Fiscal Year
2017
Total Cost
$321,281
Indirect Cost
$97,987
Name
University of Texas MD Anderson Cancer Center
Department
Obstetrics & Gynecology
Type
Other Domestic Higher Education
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
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