Ovarian cancer is the second most common gynecologic cancer. Because of low rates of survival for the majority of ovarian cancer patients, identification of factors contributing to tumor progression is of paramount importance. Epidemiologic studies have suggested an association between biobehavioral factors such as life stress, depression, and social support and cancer progression. This study examines a novel pathway that may underlie these links in ovarian cancer, specifically, the relationship of biobehavioral factors with resident macrophages within the tumor microenvironment. It is now acknowledged that the tumor microenvironment is critical in supporting or inhibiting tumor progression. We have previously reported associations of depression and low social support with a poorer cellular immune response in ovarian cancer patients in the tumor microenvironment. We have also demonstrated direct links between biobehavioral factors and cytokines supporting angiogenesis, the formation of new blood vessels that enhance tumor growth and progression. Macrophages are major components of the tumor microenvironment where they are predominantly converted from an anti-tumor phenotype to a pro-tumor phenotype and play a key role in supporting inflammation and tumor progression. However, little is known regarding whether biobehavioral factors influence tumor associated macrophages (TAM) and interactions between TAM and tumor cells in a way that favors tumor growth. Based on compelling preliminary data, we propose that biobehavioral influences on both TAM and tumor cells in the tumor microenvironment have significant effects on production of factors supporting tumor growth and progression. We focus on TAM because of their key role in the tumor microenvironment, and because of indications of macrophage sensitivity to stress factors in the cardiovascular literature and in our preliminary data. Thus, the overarching goal of this proposal is to examine pathways by which biobehavioral factors contribute to a permissive local environment for interactions between resident cells (TAM) and tumor cells that favor tumor growth in ovarian cancer. The proposed project will prospectively examine the relationship of biobehavioral factors (life stress, depression, and social support) and TAM products (inflammatory cytokines and tumor growth factors) in the tumor microenvironment in 206 ovarian cancer patients. Association of biobehavioral factors with upregulation of gene transcripts related to inflammation and proliferation in tumor cells will also be examined. Based on preliminary data we will examine the role of adrenergic signaling as a mediator in these relationships. To determine the clinical significance of these biological alterations, the investigation will assess progression-free and overall survival during the 24 months following diagnosis. Findings will have implications for innovative behavioral and pharmacological intervention strategies for ovarian cancer patients.
There has been very little research examining systemic effects on the tumor microenvironment. This research examines a novel pathway by which biobehavioral factors may contribute to a permissive milieu for tumor growth and disease progression in the tumor microenvironment among ovarian cancer patients. A clearer understanding of biobehavioral risk factors and pathways by which they operate is critical for identifying targets for psychosocial and pharmacological intervention for ovarian cancer patients who may be at risk.
| Allen, Julie K; Armaiz-Pena, Guillermo N; Nagaraja, Archana S et al. (2018) Sustained Adrenergic Signaling Promotes Intratumoral Innervation through BDNF Induction. Cancer Res 78:3233-3242 |
| Davis, Lauren Z; Cuneo, Michaela; Thaker, Premal H et al. (2018) Changes in spiritual well-being and psychological outcomes in ovarian cancer survivors. Psychooncology 27:477-483 |
| Nagaraja, Archana S; Dood, Robert L; Armaiz-Pena, Guillermo et al. (2018) Adrenergic-mediated increases in INHBA drive CAF phenotype and collagens. JCI Insight 3: |
| Armer, Jessica S; Clevenger, Lauren; Davis, Lauren Z et al. (2018) Life stress as a risk factor for sustained anxiety and cortisol dysregulation during the first year of survivorship in ovarian cancer. Cancer 124:3401-3408 |
| Lutgendorf, Susan K; Thaker, Premal H; Arevalo, Jesusa M et al. (2018) Biobehavioral modulation of the exosome transcriptome in ovarian carcinoma. Cancer 124:580-586 |
| 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 |
| 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 |
| Christensen, Desiré K; Armaiz-Pena, Guillermo N; Ramirez, Edgardo et al. (2016) SSRI use and clinical outcomes in epithelial ovarian cancer. Oncotarget 7:33179-91 |
| Nagaraja, A S; Dorniak, P L; Sadaoui, N C et al. (2016) Sustained adrenergic signaling leads to increased metastasis in ovarian cancer via increased PGE2 synthesis. Oncogene 35:2390-7 |
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