Chronic prostatitis alters the prostatic microenvironment and accelerates preneoplastic lesions in C57BL/6 mice

Abstract

Background Chronic prostatitis has been supposed to be associated with preneoplastic lesions and cancer development. The objective of this study was to examine how chronic inflammation results in a prostatic microenvironment and gene mutation in C57BL/6 mice. Methods Immune and bacterial prostatitis mouse models were created through abdominal subcutaneous injection of rat prostate extract protein immunization (EAP group) or transurethral instillation of uropathogenic E. coli 1677 ( E. coli group). Prostate histology, serum cytokine level, and genome-wide exome (GWE) sequences were examined 1, 3, and 6 months after immunization or injection. Result In the EAP and E. coli groups, immune cell infiltrations were observed in the first and last months of the entire experiment. After 3 months, obvious proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN) were observed accompanied with fibrosis hyperplasia in stroma. The decrease in basal cells (Cytokeratin (CK) 5+/p63+) and the accumulation of luminal epithelial cells (CK8+) in the PIA or PIN area indicated that the basal cells were damaged or transformed into different luminal cells. Hic1, Zfp148, and Mfge8 gene mutations were detected in chronic prostatitis somatic cells. Conclusion Chronic prostatitis induced by prostate extract protein immunization or E. coli infection caused a reactive prostatic inflammation microenvironment and resulted in tissue damage, aberrant atrophy, hyperplasia, and somatic genome mutation. Electronic supplementary material The online version of this article (10.1186/s40659-019-0237-4) contains supplementary material, which is available to authorized users.

The Crosstalk between Prostate Cancer and Microbiota Inflammation: Nutraceutical Products Are Useful to Balance This Interplay?

“…and Acidovorax spp.) in prostate specimens of African men, which were also associated with elevated tumor hypermutation, suggesting the possibility of a bacterially driven oncogenic transformation [69].…”

“…Several putative etiological agents have been identified, from the xenotropic murine leukemia virus related-virus XMRV to different strains of bacteria [58,[65][66][67]. Several studies support the potential role of infectious agents in PCa etiology with evidence that up to 87% of PCa patients show microbial DNA in their prostate [68,69]. However, if no clear association had been shown with HPV or other sexually transmitted viruses, men with previous gonorrhea or syphilis infections had a 60% increased risk of developing PCa [70].…”

Morphological and Molecular Characterization of Proliferative Inflammatory Atrophy in Canine Prostatic Samples

“…In human PC, the progression of PIA to high grade-PIN (HGPIN) and PC cancer has been described over recent years, due the role of chronic inflammation in cancer development [ 1 , 2 , 3 , 4 , 5 , 6 ]. In dogs, little is known in regard to the carcinogenic process and the progression of preneoplastic lesions to PC.…”

“…In men, PIA occurs in the peripheral zone of the prostate gland, where prostate cancer (PC) is also more commonly observed [ 4 ]. A mononuclear inflammatory infiltrate is frequently associated with PIA lesions [ 4 , 5 , 6 ] and these inflammatory cells secrete proteases, as well as mitogenic, antiapoptotic and angiogenic factors in the prostatic microenvironment [ 7 ], which ultimately induce epithelial cell atrophy, followed by cell proliferation [ 5 , 8 ]. PIA can occur adjacent to high-grade prostatic intraepithelial neoplasia (HGPIN) and prostate cancer (PC), with some studies highlighting the preneoplastic significance of PIA in human PC development [ 9 , 10 ].…”

GSTT1, an increased risk factor for prostate cancer in patients with metabolic syndrome

“…19 When local prostate tissue continues to be in a microenvironment of high oxidative stress and immune disorder, genetic instability and uncontrolled cell division in the mixture of Proliferative Inflammatory Atrophy (PIA), prostatic intraepithelial neoplasia (PIN), and inflammatory cells lead to cancer. [36][37][38] In this study, patients with Mets were diagnosed with PCa at a younger age, with higher levels of PSA and larger TPV. Moreover, our study also shows that patients with both GSTT1 null genotype and Mets are at high risk for PCa.…”