Cancer Control Research5R01CA110793-05
Sood, Anil K.
TUMOR METASTASIS: BIOBEHAVIORAL MECHANISMS
DESCRIPTION (provided by applicant): Ovarian cancer has the highest mortality rate among gynecologic malignancies. Due to poor survival of women with epithelial ovarian cancer, identification of factors responsible for accelerated cancer growth is of critical importance and may lead to development of novel therapeutic approaches. Psychosocial stress can elicit alterations of immunological, neurochemical, and endocrinological functions. To date, most of the research dealing with stress and tumor growth has focused on suppressed immunity; however, progressive growth of cancer is influenced by many other factors including tumor cell migration and invasion. There has been little investigation of the effect of stress hormones such as norepinephrine and epinephrine on these key processes that are required for metastasis. Focal adhesion kinase (FAK) is one of the key factors involved in tumor cell migration and invasion. We have compelling preliminary data that one of the stress hormones, norepinephrine, can directly activate FAK and promote tumor growth and these effects can be blocked by using inhibitors of beta-adrenergic receptors. Furthermore, our preliminary data suggest that FAK plays a key role in ovarian cancer migration and invasion. This project is designed to examine the effects of psychosocial factors and stress hormones (norepinephrine and epinephrine) on growth and progression of ovarian cancer. We have designed a series of experiments that will determine the underlying mechanisms and pathways by which stress hormones can affect ovarian cancer migration and invasion using in vitro assays and we will also experimentally determine the in vivo effects of stress on ovarian cancer progression using a well-characterized mouse model of ovarian carcinoma. Furthermore, we will examine the associations between psychosocial factors and FAK in human ovarian cancers. Findings of this study could lead to identification of novel mechanisms underlying accelerated ovarian cancer growth in a "mind-body" model of disease and therefore may lead to new behavioral and pharmacological therapeutic approaches.