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.

Public Health Relevance

These studies explore an established link between a prevalent human pathogen, Trichomonas vaginalis, and increased high-grade prostate cancer and infertility in men who have been infected with this parasite. We hypothesize that the inflammation that results from infection with T. vaginalis promotes the proliferation and tumorogenesis of prostate cells and the immobilization of human sperm. Inflammation increases the risk for developing multiple types of cancer, therefore, what is learned from these studies wil contribute to a better overall understanding of inflammation and cancer.

Agency
National Institute of Health (NIH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI105779-02
Application #
8716664
Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
David, Hagit S
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Twu, Olivia; Dessí, Daniele; Vu, Anh et al. (2014) Trichomonas vaginalis homolog of macrophage migration inhibitory factor induces prostate cell growth, invasiveness, and inflammatory responses. Proc Natl Acad Sci U S A 111:8179-84
Twu, Olivia; Johnson, Patricia J (2014) Parasite extracellular vesicles: mediators of intercellular communication. PLoS Pathog 10:e1004289