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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中最常见的非皮肤癌，也是世界上第六大常见癌症，占男性所有癌症的约10%。炎症被认为在前列腺癌的发生和发展中起重要作用;然而，炎症的来源是未知的。阴道毛滴虫是一种性传播的寄生虫，感染前列腺上皮细胞，与前列腺癌的发病率和严重程度增加呈正相关。滴虫病也与男性不育有关。我们最近发现了一种分泌型T.炎性细胞因子人巨噬细胞移动抑制因子（MIF）的迷走神经同源物。在前列腺癌和不育男性的精液中都发现了人MIF（HuMIF）水平的增加。我们假设T.迷走神经生长因子MIF（TvMIF）可以模拟人细胞因子，从而提供有助于前列腺癌的促进和进展的炎症来源。我们还假设TvMIF抑制人类精子的运动性，如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类免疫应答（目的1），表征TvMIF对前列腺细胞增殖和肿瘤发生的影响（目的2），并测试TvMIF抑制精子运动的能力（目的3）。这些研究是首次探索感染人类流行病原体T.流浪汉由此产生的数据很有可能揭示有关炎症在前列腺癌中作用的新信息。由于炎症与除前列腺癌外的其他癌症的风险增加有关（例如，食管癌、胃癌和肝癌）的研究将有助于更好地了解炎症和癌症。寄生虫蛋白质可以模拟同源宿主蛋白质的功能的观察也是令人感兴趣的，并且为探索TvMIF在调节宿主：病原体相互作用中所起的其他作用打开了大门。此外，这一探索性工作为T.阴道感染在男性和女性中都有，因为滴虫病也增加了宫颈癌的风险，并增加了妇女的不孕症。