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.
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.
|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|
Showing the most recent 10 out of 96 publications