Inflammation and prostate cancer: friends or foe?

Taverna, Gianluigi; Pedretti, Elisa; Di, Giuseppe; Borroni, Elena Monica; Marchesi, Federica; Grizzi, Fabio

doi:10.1007/s00011-015-0812-2

Cited by 54 publications

(46 citation statements)

References 133 publications

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“…A similar relationship between inflammation and carcinogenesis is found in prostate cancer (26, 109), although the association is not always consistent (74). In cases when inflammation predisposes prostate cancer, macrophage inhibitory cytokine-1 (MIC-1) expression, driven by IL-1beta and TNF-alpha pathways, is involved in the carcinogenesis (30, 54).…”

Section: The Role Of Inflammation In Cancer Initiationmentioning

confidence: 53%

Cancer and inflammation

Munn

2016

WIREs Mechanisms of Disease

204

134

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The relationship between inflammation and cancer has been recognized since the 17th century (6), and we now know much about the cells, cytokines and physiological processes that are central to both inflammation and cancer (39, 62, 66–68, 86, 92, 125). Chronic inflammation can induce certain cancers (11, 14, 27, 59, 61, 76, 79, 82), and solid tumors, in turn, can initiate and perpetuate local inflammatory processes that foster tumor growth and dissemination (7, 17, 67, 96). Consequently, inflammatory pathways have been targeted in attempts to control cancer (22, 46, 47). Inflammation is a central aspect of the innate immune system’s response to tissue damage or infection, and also facilitates the recruitment of circulating cells and antibodies of the adaptive immune response to the tissue. Components of the innate immune response carry out a robust, but sometimes overly-conservative response, sacrificing specificity for the sake of preservation. Thus, when innate immunity goes awry, it can have profound implications. How the innate and adaptive immune systems cooperate to neutralize pathogens and repair damaged tissues is still an area of intense investigation. Further, how these systems can respond to cancer, which arises from normal “self” cells that undergo an oncogenic transformation, has profound implications for cancer therapy. Recently, immunotherapies that activate adaptive immunity have shown unprecedented promise in the clinic, producing durable responses and dramatic increases in survival rate in patients with advanced stage melanoma (84, 119, 121). Consequently, the relationship between cancer and inflammation has now returned to the forefront of clinical oncology.

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Section: The Role Of Inflammation In Cancer Initiationmentioning

confidence: 53%

Cancer and inflammation

Munn

2016

WIREs Mechanisms of Disease

204

134

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“…The potential mechanistic relationships between the molecular events associated with the persistent inflammatory response and prostate carcinogenesis have important implications for optimizing the current therapies against different prostatic disorders and PC [50]. …”

Section: Resultsmentioning

confidence: 99%

Prognostic value of inflammation in prostate cancer progression and response to therapeutic: a critical review

et al. 2016

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Prostate is an immune-competent organ normally populated by inflammatory cells. Prostatic inflammation origin can be multi-factorial and there are some emerging evidences on its possible role as a factor involved in prostate cancer (PC) pathogenesis and progression.This review critically analyzes the role of inflammation as a prognostic factor for progression and aggressiveness of PC. We verified the last 10 years literature data on the association between inflammation and PC aggressiveness, or PC response to therapies.Several studies tried to correlate different inflammatory factors with the aggressiveness and metastatization of PC; all data sustain the role of inflammation in PC progression but they also produce confusion to identify a reliable clinical prognostic marker.Data on patients submitted to radical prostatectomy (RP) showed that cases with marked intraprostatic tissue inflammation are associated with higher rate of biochemical progression; systemic inflammation markers appear to have a significant prognostic value.Analyzing data on patients submitted to radiotherapy (RT) emerges a significant association between high neuthrophil to lymphocyte ratio (NLR) and decreased progression free survival and overall survival; also plateled to lymphocyte ratio (PLR) and C-reactive protein (CRP) have been proposed as significant prognostic factors for progression and overall survival.In patients submitted to androgen deprivation therapy (ADT), inflammation may drive castration resistant PC (CRPC) development by activation of STAT3 in PC cells. NLR has been proposed as independent predictor of overall survival in CRPC submitted to chemotherapy.Most of data are focused on markers related to systemic inflammation such as NLR and CRP, more than specifically to chronic prostatic inflammation. The suggestion is that these inflammatory parameters, also if not specific for prostatic inflammation and possibly influenced by several factors other than PC, can integrate with established prognostic factors.

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“…It has been postulated that, under the influence of chronic inflammation, the proliferating epithelial cells of the prostate tend to adapt to the altered microenvironment by altering the delicate balance between cell death and proliferation (29). Chronic inflammation with the accumulation of lymphocyte infiltrate in the prostate may lead to repeated tissue damage and regeneration, with release or increased expression of cytokines, growth factors, and oncogenes, leading to a highly neoplastic state (30,31). This has been observed by a marked increase in the Bcl-2 protein, a marker of cell survival, in PIA/PAH lesions by our group and several other investigators (32,33).…”

Section: Discussionmentioning

confidence: 99%

Influence of chronic inflammation on Bcl-2 and PCNA expression in prostate needle biopsy specimens

et al. 2017

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The association between inflammation and cancer has been established in certain forms of human malignancies; however, its role in prostate cancer remains unclear. The present study investigates a possible association between chronic inflammation and the development of epithelial neoplasia in the prostate. Needle biopsy specimens were obtained from patients with serum prostate-specific antigen levels >4 ng/ml, evaluated for morphological findings, and immunostained for Bcl-2 and proliferating cell nuclear antigen (PCNA). Bcl-2 is a survival protein that appears to lie at a nodal point in pathways involved in cell survival, carcinogenesis, and development of therapeutic resistance in certain cancer types. Similarly, PCNA is a critical protein for DNA replication, repair of DNA damage, chromatin structure maintenance, chromosome segregation and cell-cycle progression. The association between these two proteins was examined in prostate tissues with and without chronic inflammation, as well as tissues with and without evidence of neoplastic changes. Of the 106 needle biopsies examined, 18% exhibited atrophy with inflammation. Proliferative inflammatory atrophy/post-atrophic hyperplasia were observed in 42%, high-grade prostatic intraepithelial neoplasia (HGPIN) in 8%, prostatic adenocarcinoma in 11%, and 2% had atypical acinar proliferation suspicious for malignancy. A total of 36 specimens were stained for Bcl-2 and PCNA. Bcl-2 was expressed widely in inflammatory and epithelial tissue; however, more intense expression was observed in the areas of chronic inflammation, predominantly in infiltrating immune cells. The highest proliferation index was observed in the epithelia of HGPIN and cancer. An inverse correlation between the expression of Bcl-2 and the expression of PCNA was observed in the epithelium. The areas of chronic inflammation were associated with increased Bcl-2 expression, whereas the highly proliferative epithelium minimally expressed Bcl-2. These results suggest that Bcl-2 alters the phenotype of particular epithelial cells with a gain in neoplastic characteristics, leading to a likely precursor that may later progress into HGPIN and cancer.

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Inflammation and prostate cancer: friends or foe?

Cited by 54 publications

References 133 publications

Cancer and inflammation

Cancer and inflammation

Prognostic value of inflammation in prostate cancer progression and response to therapeutic: a critical review

Influence of chronic inflammation on Bcl-2 and PCNA expression in prostate needle biopsy specimens

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