Chronic prostate inflammation as a risk factor for prostate cancer development. Study of an animal model

Mar del Plata

Congreso; LXVI Reunión Anual de SAI, LXIII Reunión Anual de la SAIC, Reunión Anual de la SAFIS, IX Reunión Anual de la NANOMEDAR, Reunión Anual de la SAV; 2018

Prostate cancer (CaP) is the second most common type of cancer in men. It is a multifactorial disease and environmental and genetic factors are involved in his development. Epidemiological studies have suggested chronic inflammation as a major risk factor. Herein, we analyzed if chronic inflammation may have a role in prostate carcinogenesis using an animal model of chronic bacterial prostatitis.C57BL/6 male mice were transurethrally inoculated with 2x108 CFU of uropathogenic E. coli 1677 (infected) or saline (controls), euthanized at 5 days (dpi), 12 or 26 weeks (wpi) post infection, and prostate infiltrating leukocytes, histopathology and immunohistochemistry/immunofluorescence for different PCa associated lesions were performed/analyzed.Infected mice developed an acute prostate infection (5 dpi) that evolved chronic (12 and 26 wpi). Infection induced prostate inflammation. Higher counts of tissue infiltrating CD45+ leukocytes were detected at 5 dpi (p<0.05), 12 (p<0.05) and 26 wpi. Acute inflammation was shown by increased CD11b+Gr1+Ly6G+ cell infiltration, hemorrhage, cellular debris, epithelial shedding and tissue disorganization at 5 dpi. On the other hand, cell infiltrates were mostly composed of CD3+ and CD11c+ cells, accompanied with epithelial cell shedding, papillomatosis, atypical hyperplasia and dysplastic changes mimicking prostate intraepithelial neoplasia (PIN) and high grade PIN (HG-PIN) at 12 and 26 wpi (p<0.05). Early after the infection, there were not changes on the expression of VEGF (neoangiogenesis), 8-OHdG (DNA oxidation) or SMA1 (periacinar smooth muscle cells). However, the expression of these markers, which are associated to PCa development, was altered in infected mice either at 12 or 26 wpi. Strikingly, these lesions were observed close to areas with PIN and HG-PIN.Our results point out that chronic inflammation induces tissue lesions, DNA oxidative damage and neo-angiogenesis associated to pre- and neoplastic tissue changes. In conclusion, chronic inflammation could be considered as a triggering factor for PCa development.