Cancer Control Research5R01CA104825-05
Lutgendorf, Susan K.
BIOBEHAVIORAL-CYTOKINE INTERACTIONS IN OVARIAN CANCER
DESCRIPTION (provided by applicant): 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 growth and progression is of paramount importance. Although relationships between psychosocial factors and immunity have been extensively documented, there has been little investigation of relationships between psychosocial factors and cytokines involved in angiogenesis, the formation of new blood vessels that enhance tumor growth. These cytokines include Interleukin-8 (IL-8), Interleukin-12 (IL-12), Interleukin-6 (IL-6), and Vascular Endothelial Growth Factor (VEGF). VEGF, one of the key promoters of tumor angiogenesis, is associated with poorer ovarian cancer survival. VEGF is influenced by a variety of cytokines, hormones including cortisol, and by sympathetic activation. We have reported that ovarian cancer patients reporting greater social support had significantly lower serum VEGF pre-surgery, whereas those reporting greater feelings of distress had higher VEGF. Additionally, in an in vitro model, we have observed that stress hormones, such as norepinephrine, induce production of VEGF from an ovarian tumor cell line and that these tumor cells also express beta-adrenergic receptors. These effects are further augmented by cortisol. These novel findings, coupled with known hormonal modulation of other angiogenic cytokines, highlight the possibility that psychosocial factors may directly influence angiogenesis, and thus tumor progression in ovarian cancer. This 5-year prospective longitudinal study will investigate relationships among psychosocial factors and 4 angiogenic cytokines: VEGF, IL-6, IL-8, and IL-12, among 154 ovarian cancer patients in a clinical setting. We have selected these cytokines because of their critical role in ovarian cancer growth and progression. Measurements of cytokines and psychosocial factors will be taken pre-surgery and at intervals up to 9 months post-surgery; disease progression will be assessed until 18 months post-surgery. The significance of these findings is that they will investigate a novel mechanism by which biobehavioral factors in ovarian cancer patients may contribute to tumor growth and disease progression. Findings will have implications for innovative behavioral and pharmacological intervention strategies for ovarian cancer patients.