Prostatitis and Prostate Cancer Development

描述（申请人提供）：前列腺炎和前列腺癌是男性极为常见的疾病，但两者之间的关系尚不清楚。虽然急性前列腺炎被认为是感染性的，但慢性前列腺炎和慢性盆腔疼痛综合征（CP/CPPS）以及无症状炎性前列腺炎的病因尚不清楚。通过研究具有免疫耐受缺陷和自发性前列腺炎的空气缺陷小鼠，我们已经鉴定出一种新的前列腺自身抗原。此外，我们发现活检证实前列腺炎症的CP/CPPS患者对类似的人类蛋白semenogelin （Sg）具有免疫反应。这些结果为支持自身免疫作为慢性前列腺炎的潜在原因提供了新的证据。此外，通过评估对Sg的免疫反应，我们可能能够在有症状或无症状的男性中检测前列腺炎症。动物模型和临床观察表明，慢性炎症可促进某些肿瘤的发展。我们假设慢性前列腺炎有助于前列腺癌的发展。本提案的总体目标是研究：1)对前列腺自身抗原Sg的免疫反应与人类前列腺癌之间是否存在关联；2)慢性炎症是否能促进小鼠模型前列腺癌的发展。在特定目的1中，我们将确定接受前列腺活检的男性对Sg的免疫反应是否与炎症和/或前列腺癌的存在相关。在具体目的2中，我们将确定慢性前列腺炎是否可以改变前列腺癌小鼠模型中肿瘤的发展。这一建议将为慢性炎症和前列腺癌发展的作用提供见解。此外，这些结果可以为通过治疗慢性前列腺炎来预防前列腺癌提供理论依据。

DESCRIPTION (provided by applicant): Prostatitis and prostate cancer are extremely common diseases in men, but the relationship between these two diseases is unknown. While acute prostatitis is thought to be infectious in nature, the etiology of chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) and asymptomatic inflammatory prostatitis remains unclear. By studying Aire-deficient mice that have defective immune tolerance and develop spontaneous prostatitis, we have identified a novel prostate autoantigen. Moreover, we have found that CP/CPPS patients with biopsy-proven inflammation in their prostate glands possess immune responses to the analogous human protein, semenogelin (Sg). These results provide new evidence to support autoimmunity as a potential cause for chronic prostatitis. Moreover, by assessing for immune responses to Sg, we may be able to detect prostate inflammation in symptomatic or asymptomatic men. Animal models as well as clinical observations demonstrate that chronic inflammation can enhance the development or certain tumors. We hypothesize that chronic prostatitis contributes to prostate cancer development. The overall objectives of this proposal are to examine: 1) whether there is an association between an immune responses to the prostate autoantigen Sg and prostate cancer in humans; and 2) whether chronic inflammation can enhance the development of prostate cancer in mouse models. In specific aim 1, we will determine whether immune responses to Sg are associated with the presence of inflammation and/or prostate cancer in men undergoing prostate biopsy. In the specific aim 2, we will determine whether chronic prostatitis can alter the development of tumors in mouse models of prostate cancer. This proposal will provide insight in the role of chronic inflammation and prostate cancer development. Moreover, these results could provide a rationale for prostate cancer prevention by treating chronic prostatitis.