Trichomonas vaginalis homolog of macrophage migration inhibitory factor induces prostate cell growth, invasiveness, and inflammatory responses.
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.
Molecular Biology Institute.
Olivia
O
Twu
Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, 07100 Sassari, Italy; and.
Daniele
D
Dessí
Department of Microbiology, Immunology, and Molecular Genetics, and.
Anh
A
Vu
Department of Microbiology, Immunology, and Molecular Genetics, and.
Frances
F
Mercer
Department of Microbiology, Immunology, and Molecular Genetics, and.
Grant C
GC
Stevens
Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús, 1650 Chascomús, Argentina.
Natalia
N
de Miguel
Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, 07100 Sassari, Italy; and.
Paola
P
Rappelli
Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, 07100 Sassari, Italy; and.
Anna Rita
AR
Cocco
Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095;
Robert T
RT
Clubb
Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, 07100 Sassari, Italy; and.
Pier Luigi
PL
Fiori
Molecular Biology Institute,Department of Microbiology, Immunology, and Molecular Genetics, and johnsonp@ucla.edu.
Patricia J
PJ
Johnson
D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D017124:Conserved Sequence; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000276:immunology; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000469:parasitology; D008297:Male; D008969:Molecular Sequence Data; D011467:Prostate / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000469:parasitology* / Q000473:pathology; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017385:Sequence Homology; D014245:Trichomonas Infections / Q000150:complications / Q000276:immunology* / Q000469:parasitology; D014246:Trichomonas vaginalis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D008263:Macrophage Migration-Inhibitory Factors; D015800:Protozoan Proteins; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human