Inflammation, Microbiota, and Prostate Cancer

Puhr, Martin; Marzo, Angelo M. De; Isaacs, William B.; Lucia, M. Scott; Sfanos, Karen S.; Yegnasubramanian, Srinivasan; Čulig, Zoran

doi:10.1016/j.euf.2016.08.010

Cited by 45 publications

(34 citation statements)

References 78 publications

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“…Bacterial LPS can cause the activation of the nuclear factor-κB (NF-κB) pathway, which can upregulate pro-inflammatory proteins such as nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) [ 20 ]. A large amount of NO was produced by the increasing level of iNOS, and then NO contributes to the synthesis and release of inflammatory factors such as cytokines and derivatives of arachidonic acid, including PGE 2 [ 21 ], and some pro-inflammatory mediators such as TNF-α and IL [ 22 , 23 ]. In general, LPS can cause severe inflammatory reactions in the body and dramatically increase the expression of NO, TNF-α and IL-6 in RAW 264.7 macrophage [ 24 , 25 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Chemical Profiles, Anti-Inflammatory Activity, and UPLC-Q-TOF/MS-Based Metabolomics in Endotoxic Fever Rats between Synthetic Borneol and Natural Borneol

Zou

Zhang

et al. 2017

Molecules

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Natural borneol (NB, called “Bingpian”) is an important traditional Chinese medicine to restore consciousness, remove heat and relieve pain, all of which are inflammation-related diseases. Recently, due to the limited source of NB, synthetic borneol (SB) is widely used as a substitute for NB in clinics. However, little is known about the effects of SB instead of NB. Herein, the aim of the present study was to compare NB and SB on chemical profiles by gas chromatography-mass spectrometer (GC-MS) analysis, anti-inflammatory activity in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) metabolomic approaches in endotoxic fever induced in rats. Results showed that, in total, 13 volatile components could be identified in NB and SB by GC-MS analysis, in which a significant difference between them still existed. The main constituents in SB were iso-borneol and borneol, while borneol contributes to 98.96% of the amount in NB. Additionally, both NB and SB exhibited remarkable anti-inflammatory effects to reduce the level of inflammatory factors including NO, TNF-α and IL-6 in LPS-induced RAW 264.7 macrophages, and lower the high body temperature in rats with endotoxic fever induced by LPS. Moreover, it seems that NB exhibited higher efficacy than SB. The unequal bioactive efficiency between NB and SB was also indicated by means of non-targeting metabolomics. Based on UPLC-Q-TOF/MS technology, 12 biomarkers in the serum of fever rats were identified. Pathway analysis revealed that the anti-fever effect of NB and SB was related to regulating the abnormal glycerophospholipid, linoleic acid and alpha-linoleic acid metabolism pathways in the fever model. Results indicated that there was still a great difference between NB and SB involving chemical constituents, anti-inflammation activity and the ability to regulate the abnormal metabolism pathways of the fever model. Certainly, further studies are warranted to better understand the replacement rationale in medicinal application.

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Section: Discussionmentioning

confidence: 99%

Comparison of Chemical Profiles, Anti-Inflammatory Activity, and UPLC-Q-TOF/MS-Based Metabolomics in Endotoxic Fever Rats between Synthetic Borneol and Natural Borneol

Zou

Zhang

et al. 2017

Molecules

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“…This clearly suggest that, to address more efficient (immune)therapeutic approaches against PCa, a better understanding of how the PCa is able to subvert the host immune system, still remains a major issue and a clinical unmet need. Preclinical and clinical evidences suggest that chronic inflammation plays a crucial role in multiple stages of prostate cancer development [35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Prostate cancer peripheral blood NK cells show enhanced CD9, CD49a, CXCR4, CXCL8, MMP-9 production, and secrete monocyte-recruiting and polarizing factors

Baci

Gallazzi

Mortara

et al. 2020

Preprint

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ABSTRACTBackgroundNatural killer (NK) cells are effector lymphocytes of the innate immunity. Two major NK cell subsets are mostly present in the peripheral blood (pNKs): the cytotoxic CD56dimCD16+ NK cell subset (90-95% of pNKs), and the low cytotoxic, highly cytokine-producing CD56brightCD16-/low NK cell subset (5-10% of pNKs). It has been demonstrated that NK cells in peripheral blood of patients with several tumors are altered. We have shown that in NSCLC and colon cancer, tumor associated circulating NK (pTA-NK) and tumor infiltrating NK (TI-NK) are skewed towards the CD56brightCD16-/low phenotype. We have detected the production of pro-inflammatory and pro-angiogenic cytokines and chemokines. Other groups are reporting similar observations. There is still a lack of knowledge concerning the phenotype of pNK cells in prostate cancer (PCa). Here, we phenotypically and functionally characterized peripheral blood NK (pNK) from PCa patients (PCa pTA-NKs) and investigated their production of soluble factors, with endothelial cells and macrophage stimulatory action.MethodsNK cell subset distribution was investigated in the peripheral blood of PCa patients, by multicolor flow cytometry (FC) for surface antigens expression. Protein arrays were performed to characterize the secretome on FACS-sorted pNK cells. Secreted products from FACS-sorted PCa TA-NKs were used to characterize their production of pro-inflammatory molecules. Secreted products from FACS-sorted PCa pTA-NKs were also used to stimulate endothelial cells and monocytes and macrophages, determining their ability to recruit and polarize them. Alterations of endothelial cells and monocytes, following exposure to secreted products from FACS-sorted PCa pTA-NKs, was assessed by RT-PCR. To confirm these observations, secreted products from 3 different PCa (PC-3, DU-145, LNCaP) cell lines were used to assess their effects on human NK cell polarization, by multicolor flow cytometry.ResultsCirculating NK cells from prostate cancer patients have been studied before, mostly for their impaired lytic functions. However, here we are the first to report that circulating pNK cells from PCa patients acquire a CD56brightCD9+CD49a+CXCR4+ phenotype with pro-inflammatory properties. We observed a similar polarization of heathy-donor derived pNK cells exposed to secreted products of three different PCa cell lines. Increased production of CXCL8, CXCR4, MMP-9, pro-inflammatory and reduced production of TNFα, IFNγ and Granzyme-B was detected. PCa TA-NKs released factors able to support angiogenesis in vitro and increased the expression of CXCL8, ICAM-1 and VCAM-1 mRNA in endothelial cells, confirming a pro-inflammatory signature. Secretome analysis revealed the ability of PCa pTA-NKs to release pro-angiogenic cytokines/chemokines involved in monocyte recruitment and M2-like polarization. In experimental setting, secreted products from PCa pTA-NKs can recruit THP-1 monocyte and polarize THP-1-differentiated macrophage towards CD206/Arginase1/IL-10/CXCL8-expressing M2-like/TAMs.ConclusionsOur results show that PCa pTA-NKs are effector cells able to produce pro-inflammatory angiogenesis factors able to stimulate endothelial cells, attract monocytes and polarize macrophage to an M2-like type. Our data provides a rationale for the possible use of pNK profiling in clinical studies on PCaGRAPHICAL ABSTRACTGraphical Abstract:Representative cartoon illustrating the pro-angiogenic features of PCa pTA-NKs.A) direct effects of PCa pTA-NKs in supporting angiogenesis by interacting with endothelial cells. B) Proposed model for PCa pTA-NK pro-angiogenic activities via macrophage recruitment and polarization.

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“…In another animal study, a potential link between prostate inflammation and cancer has been reported (Khalili et al., ). The inflammation‐associated atrophy or proliferative inflammatory atrophy (PIA) demonstrated with prostatic chronic inflammation which has hyperproliferative nature and the hyperproliferative nature refers it may be the direct precursor lesion for prostatic intraepithelial neoplasia (PIN) and/or prostate cancer (Puhr et al., ).…”

Section: Discussionmentioning

confidence: 99%

Association between male accesory gland infections and prostate cancer in Turkish men: A case-control study

et al. 2018

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It is well known that chronic inflammation contributes to several forms of human cancer. Although several studies have investigated the association between prostatitis and prostate cancer, there is a lack of specifically designed study about male accessory gland infections (MAGI) and prostate cancer co-occurrence. We aimed to investigate this association with a case-control study in Turkish men. A total of 155 patients were enrolled to the study. After the pathological examination of the transrectal ultrasound-guided prostate biopsy specimens, patients were divided the two groups as control and prostate cancer and the presence of MAGI was determined. Of 155 patients, 145 met inclusion criteria. In the prostate cancer group, MAGI diagnose was determined in 18 of 31 patients (58.06%), while it was determined in 25 of 114 (21.93%) patients in the control group (p = .001). A significant correlation between MAGI and pathological Gleason score also revealed (p = .0001). We demonstrated that men with MAGI have increased risk for the development of prostate cancer. Moreover, in this population, most of the prostate cancers tend to be clinically significant or high grade.

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Inflammation, Microbiota, and Prostate Cancer

Cited by 45 publications

References 78 publications

Comparison of Chemical Profiles, Anti-Inflammatory Activity, and UPLC-Q-TOF/MS-Based Metabolomics in Endotoxic Fever Rats between Synthetic Borneol and Natural Borneol

Comparison of Chemical Profiles, Anti-Inflammatory Activity, and UPLC-Q-TOF/MS-Based Metabolomics in Endotoxic Fever Rats between Synthetic Borneol and Natural Borneol

Prostate cancer peripheral blood NK cells show enhanced CD9, CD49a, CXCR4, CXCL8, MMP-9 production, and secrete monocyte-recruiting and polarizing factors

Association between male accesory gland infections and prostate cancer in Turkish men: A case-control study

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