Trichomonas vaginalis MIF: a role in prostate cancer and infertility?

描述(申请人提供)：前列腺癌是北美男性诊断的最常见的非皮肤癌，是世界上第六大常见癌症，约占男性所有癌症的10%。炎症被认为在前列腺癌的发生和发展中起着重要作用；然而，炎症的来源(S)尚不清楚。阴道毛滴虫是一种性传播寄生虫，感染前列腺上皮，与前列腺癌发病率和严重程度增加呈正相关。滴虫病也与男性不育症有关。我们最近发现了炎性细胞因子人巨噬细胞移动抑制因子(MIF)的分泌型阴道毛滴虫同源物。在前列腺癌和不育男性的精液中都发现人类MIF(HuMIF)水平升高。我们假设阴道毛滴虫MIF(TvMIF)可以模拟人类细胞因子，从而提供促进前列腺癌发展的炎症来源。我们还假设TvMIF抑制人类精子的活力，就像HuMIF所示，导致不育。我们的目标是测试TvMIF是否通过诱导促炎细胞因子影响人体免疫反应(目标1)，表征TvMIF对前列腺细胞增殖和肿瘤发生的影响(目标2)，并测试TvMIF抑制精子运动的能力(目标3)。这些研究是第一次探索 感染人类流行病原体阴道毛滴虫的男性前列腺癌和不孕症增加的分子基础。由此产生的数据很有可能揭示有关炎症在前列腺癌中的作用的新信息。因为炎症与前列腺癌以外的其他癌症的风险增加有关(例如，食道癌、胃癌和肝癌)从这项研究中学到的东西将有助于更好地了解炎症和癌症的一般情况。寄生虫蛋白可以模拟同源宿主蛋白的功能的观察也是有趣的，并为探索TvMIF在调节宿主：病原体相互作用中发挥的其他作用打开了大门。此外，这项探索性工作为继续分析男性和女性阴道毛滴虫感染中的TvMIF奠定了基础，因为滴虫病还会增加患宫颈癌的风险，并增加女性的不孕不育。

DESCRIPTION (provided by applicant): Prostate cancer is the most common non-skin cancer diagnosed in North American men and is the sixth most common cancer in the world, accounting for ~10% of all cancers in men. Inflammation is thought to play an important role in the initiation and progression of prostate cancer; however, the source(s) of inflammation are unknown. Trichomonas vaginalis, a sexually-transmitted parasite, infects prostate epithelium and is positively associated with increased incidence and severity of prostate cancer. Trichomoniasis is also associated with infertility in men. We have recently identified a secreted T. vaginalis homologue of the inflammatory cytokine, human macrophage migration inhibitory factor (MIF). Increased level of human MIF (HuMIF) have been found in both prostate cancer and the semen of infertile men. We hypothesize that T. vaginalis MIF (TvMIF) can mimic the human cytokine thereby providing a source of inflammation that contributes to the promotion and progression of prostate cancer. We also hypothesize that TvMIF inhibits the motility of human sperm, as shown for HuMIF, contributing to infertility. Our objectives are to test whether TvMIF effects the human immune response by inducing pro-inflammatory cytokines (Aim 1), characterize the effect of TvMIF on prostate cell proliferation and tumorogenesis (Aim 2) and to test the ability of TvMIF to inhibit sperm motility (Aim 3). These studies are the first to explore the molecular basis of increased prostate cancer and infertility in men infected with the prevalent human pathogen, T. vaginalis. The resulting data have a high probability of revealing new information on the role of inflammation in prostate cancer. As inflammation has been associated with enhanced risk for other cancers in addition to prostate cancer (eg. eosophageal, gastric and liver cancers) what is learned from this study will contribute to a better understanding of inflammation and cancer in general. The observation that a parasite protein can mimic the function of the homologous host protein is also of interest and opens doors to explore additional roles TvMIF plays in modulating host:pathogen interactions. Moreover, this exploratory work sets the stage for continued analyses of TvMIF in T. vaginalis infections in both men and women, as trichomoniasis also increases the risk of cervical cancer and enhances infertility in women.