Abstract
Inflammation has been suggested to play an important role in onset and progression of prostate cancer (PCa). Histological analysis of prostatectomy specimens has revealed focal inflammation in early stage lesions of this malignancy. We addressed the role of inflammatory stimuli in the release of PCa-specific, tumor-derived soluble factors (PCa-TDSFs) already reported to be mediators of PCa morbidity, such as indoleamine 2,3-dioxygenase (IDO) and interleukin (IL)-6. Inflammation-driven production and functions of PCa-TDFSs were tested “in vitro” by stimulating established cell lines (CA-HPV-10 and PC3) with IFN-γ or TNF-α. Expression of genes encoding IDO, IL-6, IFN-γ, TNF-α, and their receptors was investigated in tumor tissues of PCa patients undergoing radical prostatectomy, in comparison with benign prostatic hyperplasia (BPH) specimens. IFN-γ and TNF-α-treatment resulted in the induction of IDO and IL-6 gene expression and release in established cell lines, suggesting that the elicitation of PCa-TDSFs by these cytokines might contribute to progression of cancer into an untreatable phenotype. An analysis based on timing of biochemical recurrence revealed the prognostic value of IDO but not IL-6 gene expression in predicting recurrence-free survival in patients (RFS) with PCa. In addition, a urine-based mRNA biomarker study revealed the diagnostic potential of IDO gene expression in urines of men at risk of PCa development.
Highlights
Chronic inflammation is considered an “enabling” characteristic of human cancers [1], its prognostic significance in malignancies of different histological origin is debated [2]
To obtain an insight into their potential relevance in prostate cancer (PCa), we analyzed the expression of genes encoding these cytokines in tissue specimens from 64 patients collected after radical prostatectomy (RP) for primary PCa
IFN-γ gene was expressed in 78 and 63% of cases, respectively (p = 0.1), whereas TNF-α gene expression was detected in 97% of PCa tissues and 90% of benign prostatic hyperplasia (BPH) tissues (p = 0.1) (Table 1)
Summary
Chronic inflammation is considered an “enabling” characteristic of human cancers [1], its prognostic significance in malignancies of different histological origin is debated [2]. Histological analysis of prostate cancer (PCa) samples consistently indicates that inflammation might play a key role in the progression of this tumor [3]. PCa is more frequent in demographic groups with high prevalence of prostatic inflammation [4], with a higher risk for obese men [5, 6]. In. IFN-γ- and TNF-α-Driven PCa Progression addition, prostate adenocarcinoma outgrowth is frequently detected in tissue areas adjacent to chronic inflammation [3, 4]. Other studies suggest that histologically detectable prostate inflammation associates with decreased PCa risk [7, 8]
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