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Trichomonas vaginalis homolog of macrophage migration inhibitory factor induces prostate cell growth, invasiveness, and inflammatory responses

Twu, Olivia and Dessì, Daniele and Vu, Anh and Mercer, Frances and Stevens, Grant C. and De Miguel, Natalia and Rappelli, Paola and Cocco, Anna Rita and Clubb, Robert T. and Fiori, Pier Luigi and Johnson, Patricia J. (2014) Trichomonas vaginalishomolog of macrophage migration inhibitory factor induces prostate cell growth, invasiveness, and inflammatory responses. Proceedings of The National Academy of Sciences, Vol. 111 (22), p. 8179-8184. eISSN 1091-6490. Article.

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DOI: 10.1073/pnas.1321884111

Abstract

The human-infective parasite Trichomonas vaginalis causes the most prevalent nonviral sexually transmitted infection worldwide. Infections in men may result in colonization of the prostate and are correlated with increased risk of aggressive prostate cancer. We have found that T. vaginalis secretes a protein, T. vaginalis macrophage migration inhibitory factor (TvMIF), that is 47% similar to human macrophage migration inhibitory factor (HuMIF), a proinflammatory cytokine. Because HuMIF is reported to be elevated in prostate cancer and inflammation plays an important role in the initiation and progression of cancers, we have explored a role for TvMIF in prostate cancer. Here, we show that TvMIF has tautomerase activity, inhibits macrophage migration, and is proinflammatory. We also demonstrate that TvMIF binds the human CD74 MIF receptor with high affinity, comparable to that of HuMIF, which triggers activation of ERK, Akt, and Bcl-2–associated death promoter phosphorylation at a physiologically relevant concentration (1 ng/mL, 80 pM). TvMIF increases the in vitro growth and invasion through Matrigel of benign and prostate cancer cells. Sera from patients infected with T. vaginalis are reactive to TvMIF, especially in males. The presence of anti-TvMIF antibodies indicates that TvMIF is released by the parasite and elicits host immune responses during infection. Together, these data indicate that chronic T. vaginalis infections may result in TvMIF-driven inflammation and cell proliferation, thus triggering pathways that contribute to the promotion and progression of prostate cancer.

Item Type:Article
ID Code:10202
Status:Published
Refereed:Yes
Uncontrolled Keywords:Prostate cancer, Trichomonas vaginalis macrophage migration inhibitory factor (TvMIF), cell proliferation
Subjects:Area 06 - Scienze mediche > MED/07 Microbiologia e microbiologia clinica
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Biomediche
Publisher:The National Academy of Sciences of the USA
eISSN:1091-6490
Deposited On:23 Oct 2014 09:40

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