The role of microorganisms in prostate cancer development

Abstract: Prostate cancer is the most common cancer among Swedish men, but the aetiology of this disease is largely unknown. There is evidence for a linkage between chronic inflammation and prostate cancer. The mechanisms causing prostate inflammation and how this could promote tumour development and progression are however largely unknown. Chronic inflammatory infiltrates are common findings in prostate tissue samples and infection is proposed to be one possible cause for this inflammation. Inflammatory cells release free radicals, cytokines, and growth factors that facilitate increased cell proliferation, DNA damage, mutations, and angiogenesis. However, the present literature on the presence of microbes in prostate tissue and their possible linkage to inflammation and cancer development is limited. Therefore, the aim of this thesis was to investigate if microorganisms are present in prostate tissue and to evaluate their role in inducing prostatitis and prostate epithelial neoplasia.The presence of microorganisms (virus, bacteria and fungi) was studied in clinical prostate tissue samples to evaluate whether or not the occurrences of microorganisms were different in patients that later developed cancer compared with matched controls that did not. Viruses, bacteria and fungi were found in prostate tissues. Out of eight different viruses investigated, EBV and JC virus were detected, but there were no differences in occurrence in the case group compared to the control group. The fungus Candida albicans was present in a very small proportion of the prostate tissue samples. The predominant bacterium was Propionibacterium acnes and the second most prevalent was Escherichia coli. The presence of Propionibacterium acnes was associated with inflammation and subsequent prostate cancer development. Propionibacterium acnes was further evaluated for its capacity to induce an inflammatory response both in vitro and in vivo. Live Propionibacterium acnes induced a strong immune reaction in prostate epithelial cells in vitro with up-regulation of inflammatory genes and secretion of pro-inflammatory cytokines. Infection with Propionibacterium acnes in rat prostate resulted in a lobe specific inflammation with the most intense inflammation in the dorso-lateral prostate, lasting up to 3 months post-inoculation. Propionibacterium acnes inflammation was also associated with altered epithelial cell morphology, signs of DNA damage and increased cell proliferation.Taken together, this thesis shows that different viruses and bacteria can be found in prostate tissue. Propionibacterium acnes, the most abundant among the bacteria detected and more prevalent in the cancer than in the control group, exhibits strong prostatitis promoting properties both in vitro and in vivo. In addition, Propionibacterium acnes can induce some of the epithelial changes known to occur during prostate neoplasia formation. This thesis therefore suggests that Propionibacterium acnes induced chronic prostatitis could promote prostate cancer development. Further studies are needed to elucidate the molecular interplay linking Propionibacterium acnes induced inflammation and the formation of a pre-neoplastic state that could evolve into prostate cancer.