Current Knowledge of the Potential Links between Inflammation and Prostate Cancer

Cai, Tommaso; Santi, Raffaella; Tamanini, Irene; Galli, Ilaria Camilla; Perletti, Gianpaolo; Johansen, Truls E. Bjerklund; Nesi, Gabriella

doi:10.3390/ijms20153833

Cited by 72 publications

(73 citation statements)

References 74 publications

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“…Inflammation also commonly occurs in the general population with or without clinical prostatitis and in benign prostatic hyperplasia. The mechanism of how benign hyperplasia‐related inflammation differs from inflammation in prostate cancer is still unclear, but a difference was found in inflammatory cell types and proportions between the two entities 43 . Again, our study showed an inverse relationship of both chronic and acute inflammation to cancer, suggesting that the CAM‐cancer association is not driven by CAM being associated with inflammation.…”

Section: Discussionmentioning

confidence: 48%

“…This may have confounded results in previous studies on the relationship between inflammation and cancer. Pathologists do not routinely report the presence and degree of inflammation and atrophy, and those who do, use various grading systems 43,49 . For assessing CAM, the difference between CAM 0 to 1 and CAM 2 to 3 is simple and reproducible in routine practice, that is, <5% vs ≥5% presence.…”

Section: Discussionmentioning

confidence: 99%

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Corpora amylacea in benign prostatic acini are associated with concurrent, predominantly low‐grade cancer

Palangmonthip

Tarima

et al. 2020

The Prostate

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Background: Corpora amylacea (CAM), in benign prostatic acini, contain acutephase proteins. Do CAM coincide with carcinoma?Methods: Within 270 biopsies, 83 prostatectomies, and 33 transurethral resections (TURs), CAM absence was designated CAM 0; corpora in less than 5% of benign acini: CAM 1; in 5% to 25%: CAM 2; in more than 25%: CAM 3. CAM were compared against carcinoma presence, clinicopathologic findings, and grade groups (GG) 1 to 2 vs 3 to 5.The frequency of CAM according to anatomic zone was counted. A pilot study was conducted using paired initial benign and repeat biopsies (33 benign, 24 carcinoma).Results: A total of 68.9% of biopsies, 96.4% of prostatectomies, and 66.7% of TURs disclosed CAM. CAM ≥1 was common at an older age (P = .019). In biopsies, 204 cases (75%) had carcinoma; and CAM of 2 to 3 (compared to 0-1) were recorded in 25.0% of carcinomas but only 7.4% of benign biopsies (P = .005; odds ratio [OR] = 5.1). CAM correlated with high percent Gleason pattern 3, low GG (P = .035), and chronic inflammation (CI). CI correlated inversely with carcinoma (P = .003). CAM disclosed no association with race, body mass index, serum prostate specific antigen (PSA), acute inflammation (in biopsies), atrophy, or carcinoma volume.With CAM 1, the odds of GG 3 to 5 carcinoma, by comparison to CAM 0, decreased more than 2× (OR = 0.48; P = .032), with CAM 2, more than 3× (OR = 0.33; P = .005), and with CAM 3, almost 3× (OR = 0.39, P = .086). For men aged less than 65, carcinoma predictive model was: Score = (2 × age) + (5 × PSA) − (20 × degree of CAM); using our data, area under the ROC curve was 78.17%. When the transition zone was involved by cancer, it showed more CAM than in cases where it was uninvolved (P = .012); otherwise zonal distributions were similar.In the pilot study, CAM ≥1 predicted carcinoma on repeat biopsy (P < .05; OR = 8), as did CAM 2 to 3 (P < .0001; OR = 30). CI was not significant, and CAM retained significance after adjusting for CI. Conclusion: CAM correlate with carcinoma. Whether abundant CAM in benign biopsies adds value amidst high clinical suspicion, warrants further study. K E Y W O R D S corpora amylacea, inflammation, peripheral zone, prediction of cancer, prostate cancer, transition zone 688 | PALANGMONTHIP ET AL.

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Section: Discussionmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Corpora amylacea in benign prostatic acini are associated with concurrent, predominantly low‐grade cancer

Palangmonthip

Tarima

et al. 2020

The Prostate

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“…Prostatic inflammation is common in prostate diseases [7][8][9]25 and it may facilitate cellular proliferation in both benign and malignant conditions. Huang et al 26 reported that mRNA and protein levels of iNOS were significantly increased in the prostate cancer and BPH with histological-prostatitis groups compared to the BPH group, which play important roles in the development and progression of prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

Mangosteen pericarp components alleviate progression of prostatic hyperplasia and mitochondrial dysfunction in rats

Tsai

Lin

et al. 2020

Sci Rep

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prostatic hyperplasia, characterized by progressive hyperplasia of glandular and stromal tissues, is the most common proliferative abnormality of the prostate in aging men. A high-fat diet (HfD) usually is a major factor inducing oxidative stress, inflammation, and an abnormal state of the prostate. Mangosteen pericarp powder (Mpp) has abundant xanthones which can be antioxidant, anti-inflammatory, and antiproliferative agents. Therefore, the purpose of this study was to research whether MPP supplementation can affect the progression of prostatic hyperplasia. Twenty-four male F344 rats were randomly divided into four groups, including a control group (C), prostatic hyperplasiainduced group (p), prostatic hyperplasia-induced with low-dose Mpp group (pL), and induced with high-dose Mpp group (pH). the p, pL, and pH groups were given weekly intraperitoneal injections of 3,2′-dimethyl-4-aminobiphenyl (DMAB) at 25 mg/kg body weight for 10 weeks, and simultaneously fed an HFD for 24 weeks. Our findings first demonstrated that MPP consumption significantly decreased the prostate weight, serum testosterone and dihydrotestosterone concentrations, protein expression of proliferating cell nuclear antigen, and malondialdehyde levels and ameliorated mitochondrial function in prostatic tissues. these results suggest that Mpp supplementation could be used to attenuate the progression of prostatic hyperplasia. Prostatic hyperplasia is a common urologic disease that mostly affects elderly men, and it is classified as benign prostatic hyperplasia (BPH) or prostate cancer based on its severity. BPH, characterized by progressive hyperplasia of glandular and stromal tissues, is the most common proliferative abnormality of the prostate in aging men. Although research indicated that the prostate size is positively associated with increasing age 1 , pathologically, BPH presents as enlarged epithelial cells and stromal cells in the prostate. Prostatic hyperplasia has negative impacts on a patient's quality of life because prostatic hyperplasia usually induces lower urinary tract symptoms, including increased frequency of urination, increased urgency of urination, painful urination, and excessive passage of urine at night 2,3. Several factors were suggested to be associated with prostatic hyperplasia development, including oxidative stress 4-6 , inflammatory mediators 7-9 , and androgens whose abnormally increased levels can cause increased oxidative stress and immoderate expressions of growth factors which play crucial roles in the progression of prostatic hyperplasia 10-12. Oxidative stress is a cellular condition which occurs when there is an imbalance between the production and clearance of reactive oxygen species (ROS). In addition, mitochondrial DNA (mtDNA) mutations may inhibit oxidative phosphorylation, increase ROS generation, and thus lead to cell proliferation and tumor growth of the prostate gland 13. The probability of mtDNA mutations in the prostate gland increase as people get older 14. In addition, consumption of a high-fa...

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“…p62 is predicted to activate HIF1A, NFκB1, NFKBIA, NFκB (complex), RELA, and SQSTM1(p62) signaling and regulate the activation of IL-1β signaling and the inhibition of NR3C1 function gene set encodes for activation and enrichment of inflammatory pathways like IL-1, IL-8, IL-6, interferon, and TNF receptor signaling. Importantly, inflammatory signaling promotes BCa [9] and PCa [71] progression. We also used IPA to identify cancer-specific networks encoded by the 350 gene set that also include p62 and SOX9 as downstream target signaling molecules and found that IL-1 is predicted to activate molecular programs similar to CTNNB1, Fibroblast Growth Factor (FGF2), and Tumor Necrosis Factor (TNF).…”

Section: Discussionmentioning

confidence: 99%

IL-1-conferred gene expression pattern in ERα+ BCa and AR+ PCa cells is intrinsic to ERα− BCa and AR− PCa cells and promotes cell survival

et al. 2020

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Background: Breast (BCa) and prostate (PCa) cancers are hormone receptor (HR)-driven cancers. Thus, BCa and PCa patients are given therapies that reduce hormone levels or directly block HR activity; but most patients eventually develop treatment resistance. We have previously reported that interleukin-1 (IL-1) inflammatory cytokine downregulates ERα and AR mRNA in HR-positive (HR +) BCa and PCa cell lines, yet the cells can remain viable. Additionally, we identified pro-survival proteins and processes upregulated by IL-1 in HR + BCa and PCa cells, that are basally high in HR − BCa and PCa cells. Therefore, we hypothesize that IL-1 confers a conserved gene expression pattern in HR + BCa and PCa cells that mimics conserved basal gene expression patterns in HR − BCa and PCa cells to promote HR-independent survival and tumorigenicity. Methods: We performed RNA sequencing (RNA-seq) for HR + BCa and PCa cell lines exposed to IL-1 and for untreated HR − BCa and PCa cell lines. We confirmed expression patterns of select genes by RT-qPCR and used siRNA and/or drug inhibition to silence select genes in the BCa and PCa cell lines. Finally, we performed Ingenuity Pathway Analysis (IPA) and used the gene ontology web-based tool, GOrilla, to identify signaling pathways encoded by our RNA-seq data set. Results: We identified 350 genes in common between BCa and PCa cells that are induced or repressed by IL-1 in HR + cells that are, respectively, basally high or low in HR − cells. Among these genes, we identified Sequestome-1 (SQSTM1/p62) and SRY (Sex-Determining Region Y)-Box 9 (SOX9) to be essential for survival of HR − BCa and PCa cell lines. Analysis of publicly available data indicates that p62 and SOX9 expression are elevated in HR-independent BCa and PCa sublines generated in vitro, suggesting that p62 and SOX9 have a role in acquired hormone receptor independence and treatment resistance. We also assessed HR − cell line viability in response to the p62-targeting drug, verteporfin, and found that verteporfin is cytotoxic for HR − cell lines. Conclusions: Our 350 gene set can be used to identify novel therapeutic targets and/or biomarkers conserved among acquired (e.g. due to inflammation) or intrinsic HR-independent BCa and PCa.

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Current Knowledge of the Potential Links between Inflammation and Prostate Cancer

Cited by 72 publications

References 74 publications

Corpora amylacea in benign prostatic acini are associated with concurrent, predominantly low‐grade cancer

Corpora amylacea in benign prostatic acini are associated with concurrent, predominantly low‐grade cancer

Mangosteen pericarp components alleviate progression of prostatic hyperplasia and mitochondrial dysfunction in rats

IL-1-conferred gene expression pattern in ERα+ BCa and AR+ PCa cells is intrinsic to ERα− BCa and AR− PCa cells and promotes cell survival

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