Expression of adenosine receptor subclasses in malignant and adjacent normal human prostate tissues

Mousavi, Seyed Ahmad; Panjehpour, Mojtaba; Izadpanahi, Mohammad Hossein; Aghaei, Mahmoud

doi:10.1002/pros.22955

Cited by 27 publications

(21 citation statements)

References 64 publications

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“…It has been documented that the expression level of A2bR was the highest among the four adenosine receptor subtypes in different ovarian and prostate cancer cell lines [ 9 , 13 ]. Similarly, compared to the adjacent normal tissues, the mean expression of A2bR was increased in diverse human cancers, including ovarian, lung, liver, oral, colon and prostate cancers [ 9 , 10 , 14 – 17 ]. In addition, high A2bR expression in triple negative breast cancer was significantly associated with poor prognosis [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…Adenosine acts its biological functions via four subtypes of adenosine receptors (ARs), A1, A2a, A2b, and A3 [ 8 ]. Recently, studies indicated that A2b receptor (A2bR) was highly expressed in various tumors due to the hypoxic environments of solid tumors [ 9 , 10 ]. Suppression of A2bR expression with shRNA was observed to significantly inhibit cell proliferation in oral cancer [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

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The adenosine A2b receptor promotes tumor progression of bladder urothelial carcinoma by enhancing MAPK signaling pathway

et al. 2017

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The adenosine A2b receptor (A2bR) was considered to play an oncogenic role in many human malignancies. However, the expression and molecular function of A2bR in bladder urothelial carcinoma (BUC) have not been well elucidated. Herein, we found that the expression of A2bR was higher than other adenosine receptors in BUC tissues and cells, and it was upregulated in BUC tissues compared with matched normal bladder tissues. Furthermore, high expression of A2bR was associated with poor prognosis of patients with BUC. In addition, suppression of A2bR inhibited the proliferation, migration and invasion of BUC cells and arrested the cell cycle at the G1 phase. Finally, we demonstrated that downregulation of A2bR inhibited the proliferation, migration and invasion of BUC in part via the MAPK signaling pathway, increasing the levels of P21 but decreasing the levels of cyclin B1, D, E1, MMP-2 and MMP-9. Overexpression of MMP-2 could rescue BUC cells migration and invasion. Thus, the present study indicates that A2bR may play a potential oncogenic role in BUC progression and act as a potential biomarker to identify BUC patients with poor clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The adenosine A2b receptor promotes tumor progression of bladder urothelial carcinoma by enhancing MAPK signaling pathway

et al. 2017

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“…45 The latter would be present at higher levels in prostate cancer tissues than in control ones; one of them, the A 2B , was reported to specifically promote prostate cancer cell growth. 44 This pathway therefore can be proposed as a novel target for prostate cancer treatment and represents a possible mechanism to explain the protective role of caffeine in the present study.…”

Section: Cancer Epidemiologymentioning

confidence: 66%

Reduction by coffee consumption of prostate cancer risk: Evidence from the Moli‐sani cohort and cellular models

Pounis

Tabolacci

Costanzo

et al. 2017

Intl Journal of Cancer

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Meta-analytic data on the effect of coffee in prostate cancer risk are controversial. Caffeine as a bioactive compound of coffee has not yet been studied in deep in vitro. Our study aimed at evaluating in a population cohort the effect of Italian-style coffee consumption on prostate cancer risk and at investigating in vitro the potential antiproliferative and antimetastatic activity of caffeine on prostate cancer cell lines. 6,989 men of the Moli-sani cohort aged ≥50 years were followed for a mean of 4.24 ± 1.35 years and 100 new prostate cancer cases were identified. The European Prospective Investigation into Cancer and Nutrition-Food Frequency Questionnaire was used for the dietary assessment and the evaluation of Italian-style coffee consumption. Two human prostate cancer cell lines, PC-3 and DU145, were tested with increasing concentrations of caffeine, and their proliferative/metastatic features were evaluated. The newly diagnosed prostate cancer participants presented lower coffee consumption (60.1 ± 51.3 g/day) compared to the disease-free population (74.0 ± 51.7 g/day) (p < 0.05). Multiadjusted analysis showed that the subjects at highest consumption (>3 cups/day) had 53% lower prostate cancer risk as compared to participants at the lowest consumption (0-2 cups/day) (p = 0.02). Both human prostate cancer cell lines treated with caffeine showed a significant reduction in their proliferative and metastatic behaviors (p < 0.05). In conclusion, reduction by Italian-style coffee consumption of prostate cancer risk (>3 cups/day) was observed in epidemiological level. Caffeine appeared to exert both antiproliferative and antimetastatic activity on two prostate cancer cell lines, thus providing a cellular confirmation for the cohort study results.

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“…A 2B AR expression at both the mRNA and protein level is higher in malignant prostate cancer tissue from human patients when compared with normal control prostate tissue (Mousavi et al, 2015). In addition, the A 2B AR has been implicated in cell proliferation and angiogenesis, accounting for its apparent role in the pathogenesis of a number of solid tumors (Li et al, 2005;Ryzhov et al, 2008;Ma et al, 2010;Cekic et al, 2012;Iannone et al, 2013;Wei et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…The A 2B AR is a pleiotropically coupled GPCR, signaling via both G s and G q proteins (Linden et al, 1999;Fredholm et al, 2001a), and represents a key example of a highly dynamic GPCR whose expression is modified by disease. The A 2B AR is significantly upregulated by HIF-1a in a number of cancers (Li et al, 2005), including human prostate cancer (Wei et al, 2013;Mousavi et al, 2015). Until recently, the A 2B AR was presumed to have minor physiologic significance, in part due to its relatively low affinity for the endogenous agonist adenosine (Feoktistov and Biaggioni, 1997;Fredholm et al, 2001b).…”

Section: Introductionmentioning

confidence: 99%

Ligand-Independent Adenosine A2B Receptor Constitutive Activity as a Promoter of Prostate Cancer Cell Proliferation

Vecchio

Tan

Gregory

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Aberrant ligand-independent G protein-coupled receptor constitutive activity has been implicated in the pathophysiology of a number of cancers. The adenosine A 2B receptor (A 2B AR) is dynamically upregulated under pathologic conditions associated with a hypoxic microenvironment, including solid tumors. This, in turn, may amplify ligand-independent A 2B AR signal transduction. The contribution of A 2B AR constitutive activity to disease progression is currently unknown yet of fundamental importance, as the preferred therapeutic modality for drugs designed to reduce A 2B AR constitutive activity would be inverse agonism as opposed to neutral antagonism. The current study investigated A 2B AR constitutive activity in a heterologous expression system and a native 22Rv1 human prostate cancer cell line exposed to hypoxic conditions (2% O 2 ). (4-chlorophenyl)piperazide-1-sulfonyl)phenyl)-1-propylxanthine), mediated a concentration-dependent decrease in baseline cAMP levels in both cellular systems. Proliferation of multiple prostate cancer cell lines was also attenuated in the presence of PSB-603. Importantly, both the decrease in baseline cAMP accumulation and the reduction of proliferation were not influenced by the addition of adenosine deaminase, demonstrating that these effects are not dependent on stimulation of A 2B ARs by the endogenous agonist adenosine. Our study is the first to reveal that wild-type human A 2B ARs have high constitutive activity in both model and native cells. Furthermore, our findings demonstrate that this ligand-independent A 2B AR constitutive activity is sufficient to promote prostate cancer cell proliferation in vitro. More broadly, A 2B AR constitutive activity may have wider, currently unappreciated implications in pathologic conditions associated with a hypoxic microenvironment.

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Expression of adenosine receptor subclasses in malignant and adjacent normal human prostate tissues

Cited by 27 publications

References 64 publications

The adenosine A2b receptor promotes tumor progression of bladder urothelial carcinoma by enhancing MAPK signaling pathway

The adenosine A2b receptor promotes tumor progression of bladder urothelial carcinoma by enhancing MAPK signaling pathway

Reduction by coffee consumption of prostate cancer risk: Evidence from the Moli‐sani cohort and cellular models

Ligand-Independent Adenosine A2B Receptor Constitutive Activity as a Promoter of Prostate Cancer Cell Proliferation

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