Adenosine stimulation of the proliferation of colorectal carcinoma cell lines

Mujoomdar, Michelle; Hoskin, David W.; Blay, Jonathan

doi:10.1016/s0006-2952(03)00548-3

Cited by 57 publications

(63 citation statements)

References 46 publications

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“…In our growth experiments, the observed changes were small, typically 30-40% in the presence of NECA or CGS21680 for BON-1 cells. These values are in line with those reported for the growth effects of 30 μM adenosine on HT-29 colectoral carcinoma and MCF-7 breast carcinoma cells over an incubation time of 8-10 days [41,42]. As for HT-29 cells [41], prolonged agonist exposure (10-12 days) could perhaps lead to markedly greater growth effects in our experiments.…”

Section: Discussionsupporting

confidence: 92%

“…These values are in line with those reported for the growth effects of 30 μM adenosine on HT-29 colectoral carcinoma and MCF-7 breast carcinoma cells over an incubation time of 8-10 days [41,42]. As for HT-29 cells [41], prolonged agonist exposure (10-12 days) could perhaps lead to markedly greater growth effects in our experiments. The affinities of adenosine for the different adenosine receptors are quite different; A 1 and A 2A being essentially high affinity (nanomolar) and the A 2B and A 3 receptors low affinity (micromolar) [12].…”

Section: Discussionsupporting

confidence: 92%

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Adenosine A2A and A2B receptor expression in neuroendocrine tumours: potential targets for therapy

Kalhan

Gharibi

Vazquez

et al. 2011

Purinergic Signalling

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The clinical management of neuroendocrine tumours is complex. Such tumours are highly vascular suggesting tumour-related angiogenesis. Adenosine, released during cellular stress, damage and hypoxia, is a major regulator of angiogenesis. Herein, we describe the expression and function of adenosine receptors (A 1 , A 2A , A 2B and A 3 ) in neuroendocrine tumours. Expression of adenosine receptors was investigated in archival human neuroendocrine tumour sections and in two human tumour cell lines, BON-1 (pancreatic) and KRJ-I (intestinal). Their function, with respect to growth and chromogranin A secretion was carried out in vitro. Immunocytochemical data showed that A 2A and A 2B receptors were strongly expressed in 15/15 and 13/18 archival tumour sections. Staining for A 1 (4/18) and A 3 (6/18) receptors was either very weak or absent. In vitro data showed that adenosine stimulated a three-to fourfold increase in cAMP levels in BON-1 and KRJ-1 cells. The non-selective adenosine receptor agonist (adenosine-5′N-ethylcarboxamide, NECA) and the A 2A R agonist (CGS21680) stimulated cell proliferation by up to 20-40% which was attenuated by A 2B (PSB603 and MRS1754) and A 2A (SCH442416) receptor selective antagonists but not by the A 1 receptor antagonist (PSB36). Adenosine and NECA stimulated a twofold increase in chromogranin A secretion in BON-1 cells. Our data suggest that neuroendocrine tumours predominantly express A 2A and A 2B adenosine receptors; their activation leads to increased proliferation and secretion of chromogranin A. Targeting adenosine signal pathways, specifically inhibition of A 2 receptors, may thus be a useful addition to the therapeutic management of neuroendocrine tumours.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Adenosine A2A and A2B receptor expression in neuroendocrine tumours: potential targets for therapy

Kalhan

Gharibi

Vazquez

et al. 2011

Purinergic Signalling

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“…Where antagonists needed to be solubilized using a nonaqueous solvent, we used dimethyl sulfoxide such that the final concentration never exceeded 0.2% (vol/vol). Adenosine at the concentrations used in these studies does not induce apoptosis in HT-29 cells (48,72). The figures show representative results from at least three separate experiments.…”

Section: Methodsmentioning

confidence: 92%

“…This is shown by observations that adenosine-treated cells, due to downregulated DPPIV, migrate at less than half the rate of untreated cells on cellular fibronectin (72) and that the decline in ecto-ADA bound to DPPIV leads to an increase in the half-life of adenosine in HT-29 cell cultures from ϳ2 h (48) to Ͼ24 h (60). Given that adenosine is immunosuppressive, mitogenic for tumor cells, and also angiogenic (4,33,34,43,44,47,48) the latter event would have major consequences in the context of an intact tumor.…”

Section: Discussionmentioning

confidence: 99%

“…This is a consequence of changes in the rates of production and removal of adenosine that are characteristic of hypoxic tissues like those in the poorly vascularized tumor (15,31,77). The adenosine that is produced is likely to have widespread actions within the tumor, including suppression of the cell-mediated immune response (33,34,40,43,44), promotion of angiogenic activity (4), stimulation of the motility of tumor cells (82), and stimulation of tumor cell growth (47,48). We recently found that adenosine also downregulates the surface expression of DPPIV protein on HT-29 human colorectal carcinoma cells, and that this effect is accompanied by decreases in DPPIV dipeptidase activity, ADA binding, adhesion to fibronectin, and cellular motility (72).…”

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confidence: 99%

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Adenosine downregulates DPPIV on HT-29 colon cancer cells by stimulating protein tyrosine phosphatase(s) and reducing ERK1/2 activity via a novel pathway

Tan

Richard²,

Zhang³

et al. 2006

American Journal of Physiology-Cell Physiology

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Mechanisms and Management of Cancer Pain

Anand

2007

The Cancer Handbook

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Chronic intractable pain is experienced by an overwhelming majority of cancer patients, compromising their quality of life. The pain can be due to several causes: infiltration by tumours, bone metastases, or a consequence of therapy. The mainstay of analgesia has been opioid treatment of various formulations, but this is limited in efficacy and is not without considerable side effects. Recent advances in understanding the underlying pathophysiological and molecular mechanisms of cancer pain have been derived from animal models and related histopathological findings from chronic pain patients. The identification of novel drug targets, and their imminent clinical trials, provides the prospect of new treatments for alleviating cancer pain in the near future.

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Adenosine stimulation of the proliferation of colorectal carcinoma cell lines

Cited by 57 publications

References 46 publications

Adenosine A2A and A2B receptor expression in neuroendocrine tumours: potential targets for therapy

Adenosine A2A and A2B receptor expression in neuroendocrine tumours: potential targets for therapy

Adenosine downregulates DPPIV on HT-29 colon cancer cells by stimulating protein tyrosine phosphatase(s) and reducing ERK1/2 activity via a novel pathway

Mechanisms and Management of Cancer Pain

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