Effects of Adenosine A&lt;sub&gt;2A&lt;/sub&gt; and A&lt;sub&gt;2B&lt;/sub&gt; Receptor Activation on Signaling Pathways and Cytokine Production in Human Uroepithelial Cells

Säve, Susanne; Persson, Katarina

doi:10.1159/000317068

Cited by 11 publications

(8 citation statements)

References 48 publications

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“…2B). These data are consistent with previous reports showing the ability of submicromolar and low micromolar concentrations of NECA (26,28) and CPCA (27) to trigger cAMP accumulation via activation of low-affinity A 2B receptors on PC-3 and other cells. The presence of A 2B receptors is further supported by qPCR data showing the abundant mRNA expression for A 2B (ADORA2B), but not for other adenosine receptor subtypes in PC-3 cells (Fig.…”

Section: Treatment Of Pc3 Cells With Adenosine But Not With Other Nusupporting

confidence: 93%

“…Pretreatment of PC-3 cells with a nonselective agonist of adenosine receptors NECA (21,26) diminished their invasion by approximately 40%, whereas a general A 2 receptor agonist CPCA (capable of stimulating both A 2A and A 2B adenosine receptors; ref. 27) did not affect the numbers of invaded cells (Fig. 1B).…”

Section: Treatment Of Pc3 Cells With Adenosine But Not With Other Numentioning

confidence: 82%

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Adenosine Inhibits Tumor Cell Invasion via Receptor-Independent Mechanisms

Virtanen

Kukkonen-Macchi

Vainio

et al. 2014

Molecular Cancer Research

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Extracellular adenosine mediates diverse anti-inflammatory, angiogenic, and other signaling effects via binding to adenosine receptors, and it also regulates cell proliferation and death via activation of the intrinsic signaling pathways. Given the emerging role of adenosine and other purines in tumor growth and metastasis, this study evaluated the effects of adenosine on the invasion of metastatic prostate and breast cancer cells. Treatment with low micromolar concentrations of adenosine, but not other nucleosides or adenosine receptor agonists, inhibited subsequent cell invasion and migration through Matrigel-and laminin-coated inserts. These inhibitory effects occurred via intrinsic receptor-independent mechanisms, despite the abundant expression of A2B adenosine receptors (ADORA2B). Extracellular nucleotides and adenosine were shown to be rapidly metabolized on tumor cell surfaces via sequential ecto-5 0 -nucleotidase (CD73/NT5E) and adenosine deaminase reactions with subsequent cellular uptake of nucleoside metabolites and their intracellular interconversion into ADP/ATP. This was accompanied by concurrent inhibition of AMP-activated protein kinase and other signaling pathways. No differences in the proliferation rates, cytoskeleton assembly, expression of major adhesion molecules [integrin1b (ITGB1), CD44, focal adhesion kinase], and secretion of matrix metalloproteinases were detected between the control and treated cells, thus excluding the contribution of these components of invasion cascade to the inhibitory effects of adenosine. These data provide a novel insight into the ability of adenosine to dampen immune responses and prevent tumor invasion via two different, adenosine receptor-dependent and -independent mechanisms.Implications: This study suggests that the combined targeting of adenosine receptors and modulation of intracellular purine levels can affect tumor growth and metastasis phenotypes.

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Section: Treatment Of Pc3 Cells With Adenosine But Not With Other Nusupporting

confidence: 93%

Section: Treatment Of Pc3 Cells With Adenosine But Not With Other Numentioning

confidence: 82%

Adenosine Inhibits Tumor Cell Invasion via Receptor-Independent Mechanisms

Virtanen

Kukkonen-Macchi

Vainio

et al. 2014

Molecular Cancer Research

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“…ATP enhances spontaneous calcium activity in cultured suburothelial myofibroblasts of the human bladder, supporting the notion that suburothelial myofibroblasts are able to register bladder fullness [145]. Different signalling pathways for A 2A and A 2B adenosine receptors expressed by human uroepithelial cells were identified [598]. Mechanical stretch (which presumably leads to release of ATP) promotes contraction and proliferation of human bladder smooth muscle cells via P2X and perhaps A 1 or P2Y receptors, respectively [715].…”

Section: Healthy Bladdermentioning

confidence: 67%

Purinergic signalling in the urinary tract in health and disease

Burnstock

2013

Purinergic Signalling

140

149

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Purinergic signalling is involved in a number of physiological and pathophysiological activities in the lower urinary tract. In the bladder of laboratory animals there is parasympathetic excitatory cotransmission with the purinergic and cholinergic components being approximately equal, acting via P2X1 and muscarinic receptors, respectively. Purinergic mechanosensory transduction occurs where ATP, released from urothelial cells during distension of bladder and ureter, acts on P2X3 and P2X2/3 receptors on suburothelial sensory nerves to initiate the voiding reflex, via low threshold fibres, and nociception, via high threshold fibres. In human bladder t h e p u r i n e rg i c c o m p o n e n t o f p a r a s y m p a t h e t i c cotransmission is less than 3 %, but in pathological conditions, such as interstitial cystitis, obstructed and neuropathic bladder, the purinergic component is increased to 40 %. Other pathological conditions of the bladder have been shown to involve purinoceptor-mediated activities, including multiple sclerosis, ischaemia, diabetes, cancer and bacterial infections. In the ureter, P2X7 receptors have been implicated in inflammation and fibrosis. Purinergic therapeutic strategies are being explored that hopefully will be developed and bring benefit and relief to many patients with urinary tract disorders.

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“…The chemokine IL-8 is produced by urinary tract epithelial cells and neutrophils during inflammation (1,21) and is known to be involved in neutrophil transuroepithelial migration (14). We have previously shown that UROtsa cells grown in a monolayer produce increased IL-8 levels when stimulated for 24 h with UPEC strain IA2 (26). In the present study, increased IL-8 production in response to UPEC infection was confirmed by greater accumulation of IL-8 in the bottom well of the transwell system for infected cells than for uninfected cells.…”

Section: Discussionmentioning

confidence: 99%