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

阴道毛滴虫 MIF：在前列腺癌和不孕症中的作用？

基本信息

批准号：
8716664
负责人：
Patricia Jean Johnson
金额：
$ 19.25万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-08 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8716664
关键词：
Accounting Address Affect American Benign Prostatic Hypertrophy Cancer Biology Cell Line Cell Proliferation Cells Data Dendritic Cells Dietary Factors Epithelium Genetic Homologous Gene Human Immobilization Immune Immune response Incidence Infection Infertility Inflammation Inflammatory Inflammatory Response Lead Learning Link Male Infertility Malignant Neoplasms Malignant neoplasm of cervix uteri Malignant neoplasm of liver Malignant neoplasm of lung Malignant neoplasm of prostate Measures Mediating Migration Inhibitory Factor Mitogen-Activated Protein Kinases Molecular Neoplasms Outcome Parasites Pathogenesis Pathway interactions Play Probability Process Prostate Prostatic Proteins Research Risk Role Seminal fluid Severities Source Sperm Motility Staging Testing Trichomonas Infections Trichomonas vaginalis Woman Workplace base cancer diagnosis cancer type cell motility cytokine human disease human migration interest macrophage malignant breast neoplasm malignant stomach neoplasm men migration neutrophil novel pathogen phenylpyruvate tautomerase public health relevance sperm cell

项目摘要

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.

描述（由申请人提供）：前列腺癌是北美男性诊断出的最常见的非皮肤癌，是世界上第六个最常见的癌症，占男性所有癌症的约10％。人们认为炎症在前列腺癌的启动和发展中起着重要作用。但是，炎症的来源尚不清楚。阴道滴虫是一种性传播的寄生虫，感染了前列腺上皮，并且与前列腺癌的发病率和严重程度的增加相关。 trichomonisis也与男性不孕有关。我们最近确定了炎性细胞因子，人巨噬细胞迁移抑制因子（MIF）的阴道阴道链球菌同源物。在前列腺癌和不育男性精液中都发现了人类MIF（HUMIF）的水平升高。我们假设阴道MIF（TVMIF）可以模仿人类细胞因子，从而提供炎症来源，从而有助于促进和进展前列腺癌。我们还假设TVMIF抑制了人类精子的运动，如HUMIF所示，导致不孕症。我们的目标是测试TVMIF是否通过诱导促炎性细胞因子（AIM 1）来影响人类免疫反应（AIM 1），表征TVMIF对前列腺细胞增殖和肿瘤发生的影响（AIM 2）并测试TVMIF抑制精子运动的能力（AIM 3）。这些研究是第一个探索的研究在感染了人类病原体T.阴道的男性中，前列腺癌增加和不育的分子基础。所得数据的可能性很高，可以揭示有关炎症在前列腺癌中作用的新信息。由于炎症与其他癌症的风险相关（例如，雌激素，胃癌和肝癌），因此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。寄生虫蛋白可以模仿同源宿主蛋白的功能的观察也引起了人们的关注，并打开了探索TVMIF在调节宿主中发挥的其他作用的门：病原体相互作用。此外，这项探索性工作为在男性和女性中的T.阴道感染中继续分析TVMIF奠定了基础，因为毛肌瘤也增加了宫颈癌的风险并增强了女性不孕症。