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？

• 批准号: 8493682
• 负责人: Patricia Jean Johnson
• 金额: $ 21.71万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-08 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8493682
• 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

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.

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.炎症被认为在前列腺癌的发生和进展中发挥着重要作用。然而，炎症的来源尚不清楚。 Trichomonas vaginalis, a sexually-transmitted parasite, infects prostate epithelium and is positively associated with increased incidence and severity of prostate cancer.滴虫病还与男性不育有关。我们最近发现了一种分泌性阴道毛滴虫炎症细胞因子的同源物，即人巨噬细胞迁移抑制因子（MIF）。在前列腺癌和不育男性的精液中发现人类 MIF (HuMIF) 水平升高。 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.我们还假设 TvMIF 会抑制人类精子的活力，如 HuMIF 所示，从而导致不育。 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).这些研究首先探索 感染流行的人类病原体阴道毛滴虫的男性前列腺癌和不育症增加的分子基础。由此产生的数据很有可能揭示炎症在前列腺癌中的作用的新信息。 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.