Abstract 2472: The role of aging T-cells in prostate cancer development
| Autor: | Christopher A. Jolly, Shruti A. Apte, Robert Faris, Ramona Salcedo, Alejandra De Angulo, Cindy Chen, David Cavazos, Linda A. deGraffenried |
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| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | Cancer Research. 70:2472-2472 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am10-2472 |
| Popis: | As men age past 40, their chance of developing prostate cancer increases exponentially each year. The mechanism by which age influences the risk of prostate cancer remains largely unknown, hindering the development of effective preventive interventions. As one ages, there are significant changes in immune response regulation and outcome. This includes an age-related loss of appropriate T cell function. This loss of appropriate T cell function is associated with a change from anti-inflammatory to pro-inflammatory cytokine production as well as decreased appropriate immune surveillance. We hypothesize that one mechanism by which age increases the risk for prostate cancer may be through these alterations in immune response by the T cells. To date, the specific contribution of an aging immune system to prostate cancer initiation and progression has been difficult to determine because of the lack of appropriate model systems to evaluate this phenomena. We have recently begun studies investigating the contribution of an aging T cell population to prostate cancer progression using a highly unique and innovative animal model, the glycerol-3-phosphate acyltransferase-1 (GPAT-1) knock out mouse. The GPAT-1 KO young mouse has a T cell phenotype which mimics old wild type mice. We have recently initiated a series of in vitro studies to evaluate the effects of exposure of sera from GPAT KO mice on pro-inflammatory signaling in LNCaP prostate cancer cells. Exposure to sera from young GPAT KO mice resulted in strong induction of NF-κB activity in LNCaP cells compared to both the sera from the age-controlled wild type mice and the sera-free conditions. We are currently evaluating the significance of this NF-κB induction as well as the induction of other pro-inflammatory pathways by the GPAT KO mouse sera in promoting a more aggressive phenotype in our cancer cells. Additionally, LNCaP cells exposed to conditioned media from stimulated T-cells from the GPAT KO mice demonstrated induction of Akt phosphorylation. Previous studies have shown an important role for NF-kB and Akt in promoting inflammation and survival in prostate cancer cells. Currently, we are evaluating how GPAT KO mouse sera might promote a more aggressive phenotype in LNCaP prostate cancer cells. These studies would be the first to demonstrate a specific modulation of prostate cancer signaling by sera from mice that directly reflect an aging T cell phenotype suggesting that age-related loss of appropriate T cell function might contribute to the increased risk for prostate cancer in the elderly. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2472. |
| Databáze: | OpenAIRE |
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