Inflammation driven tumor‐like signaling in prostatic epithelial cells by sexually transmitted Trichomonas vaginalis

Abstract

Objectives To identify the sequence of inflammation‐driven signaling cascades and other molecular events that might cause tumor‐like transformation of prostatic cells. Methods Cytokine array analysis, Reactome and STRING analysis, immunoblotting, and immunocytochemistry were used to investigate the molecular mechanisms governing inflammation‐driven adverse changes in human prostatic cells caused by the sexually transmitted infection, Trichomonas vaginalis, resulting in prostatitis, benign prostatic hyperplasia and prostate cancer. Results Array analysis showed upregulation of 23 cytokines within 24 h of infection of human prostatic epithelial RWPE‐1 cells with the parasite, in vitro. Reactome and STRING analysis of array data identified interleukin‐6, interleukin‐8, nuclear factor kappa B, signal transducer and activator of transcription 3 and cyclooxygenase 2 as chief instigators of prostatic anomaly, which were found to be significantly upregulated by immunofluorescence and western blotting analyses. STRING further connected these instigators with macrophage migration inhibitory factor, PIM‐1 and prostate‐specific antigen; which was confirmed by their marked stimulation in infected prostatic cells by immunoblotting and immunocytochemistry. Upregulated proliferation markers, such as Ki67, proliferating cell nuclear antigen and B‐cell lymphoma 2, suggested tumor‐like signaling in infected RWPE‐1 cells, which was further supported by downregulation of E‐cadherin, upregulation of vimentin and activation of focal adhesion kinase. Prostate tumor DU145 cells were more sensitive to parasite invasion, and showed rapid upregulation with nuclear translocation of sensitive parameters, such as nuclear factor kappa B, signal transducer and activator of transcription 3, and macrophage migration inhibitory factor. The migration of DU145 cells augmented when incubated in spent media from parasite‐infected RWPE‐1 cells. Conclusion The initiation of inflammation driven tumor‐like cell signaling in parasite‐infected human prostatic epithelial cells is apparent, with the prostate tumor (DU145) cells being more sensitive to T. vaginalis than normal (RWPE‐1) prostatic cells.

Double-Stranded RNA Viruses Are Released From Trichomonas vaginalis Inside Small Extracellular Vesicles and Modulate the Exosomal Cargo

“…The symptomatic infections include urethritis and prostatitis, and the trichomonads have been found in prostate tissue from benign prostatic hyperplasia ( Mitteregger et al, 2012 ; Van Gerwen et al, 2021 ). Moreover, trichomoniasis is associated with an increased risk of cervical and prostate cancer and transmission of HPV and HIV, which is related to erosion of the mechanical barrier and modulation of immune status ( Kissinger and Adamski, 2013 ; Twu et al, 2014 ; Belfort et al, 2021 ; Kushwaha et al, 2021 ; Van Gerwen et al, 2021 ).…”

The correlation between Trichomonas vaginalis infection and reproductive system cancer: a systematic review and meta-analysis

“…Chronic T. vaginalis infections result in TvMIF ( T. vaginalis macrophage migration inhibitory factor)-driven inflammation and cell proliferation, thus triggering pathways that contribute to progression of prostate cancer [ 51 ]. The initiation of inflammation driven tumor-like cell signaling in parasite-infected human prostatic epithelial cells and the prostate tumor cells are more sensitive to T. vaginalis than normal prostatic cells [ 63 ]. The level of IL-6 in BPH-1 cells infected with T. vaginalis is increased, and IL-6 is considered to be a factor promoting the development of benign prostatic hyperplasia and prostate cancer [ 54 , 66 ].…”

Cell signaling in sperm midpiece ensures quiescence and survival in cauda epididymis

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