Prostate cancer is the most common non-skin cancer among men in most western populations, and it is the second leading cause of cancer death among U.S. men. Despite its high morbidity, the etiology of prostate cancer remains largely unknown. Epidemiological studies have established advancing age, race, and a family history of prostate cancer as risk factors, while many putative risk factors, including androgens, diet, physical activity, sexual factors, inflammation, and obesity have been implicated, but their roles in prostate cancer etiology remain unclear. A significant impediment to developing effective preventive approaches against prostate cancer is the lack of a clear understanding as to the mechanisms by which these risk factors influence disease development and progression. The mechanisms by which aging impacts tumorigenesis are especially understudied, due to the complexities and co-morbidities associated with the aging process. This is especially true in the case of understanding how an aging immune system modulates prostate cancer initiation and progression. Relevant models in which specific components of the aging immune system can be recapitulated are critical for delineating the relationship between aging and tumorigenesis and studying the specific mechanisms by which aging modulates the disease process. Based upon the current understanding of the role of pro-inflammatory pathways in promoting tumorigenesis and our preliminary data demonstrating an induction of these pathways in prostate cancer cells in response to sera from a model of an aging immune system, we hypothesize that the altered immune function in the aging T lymphocyte may not merely be a passive, permissive event in tumor development, but may actively contribute to and promote prostate cancer initiation and progression through changes induced in the prostate cancer microenvironment. We propose to develop a highly unique and novel transgenic animal model to investigate how an aging immune system promotes prostate cancer initiation and progression. We will then assess how the changes in T cell function associated with aging modulate prostate cancer development. This model will be an invaluable tool for developing effective approaches for prevention and treatment of this pervasive disease, and will provide significant insight into the etiology and progression of the second leading cause of cancer deaths in men in the US.
/RELEVANCE Prostate cancer is the most common non-skin cancer among men in most western populations, and it is the second leading cause of cancer death among U.S. men. Despite its high morbidity, the etiology of prostate cancer remains largely unknown. We propose to develop a highly novel model for investigating the role of an aging immune system in promoting the initiation and progression of this highly deadly disease.
|De Angulo, Alejandra; Faris, Robert; Cavazos, David et al. (2013) Age-related alterations in T-lymphocytes modulate key pathways in prostate tumorigenesis. Prostate 73:855-64|