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SHR Neuro Cancer Cardio Lipid Metab Microb

Kalhan, A; Gharibi, B; Vazquez, M; Jasani, B; Neal, J; Kidd, M; Modlin, IM; Pfragner, R; Rees, DA; Ham, J.
Adenosine A2A and A2B receptor expression in neuroendocrine tumours: potential targets for therapy.
Purinergic Signal. 2012; 8(2):265-274 Doi: 10.1007/s11302-011-9280-5 [OPEN ACCESS]
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Co-authors Med Uni Graz: Pfragner Roswitha
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Abstract:: 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.
Find related publications in this database (using NLM MeSH Indexing): Antineoplastic Agents - administration & dosage; Cell Line, Tumor -; Drug Delivery Systems - methods; Gene Expression Regulation, Neoplastic - drug effects; Humans -; Neuroendocrine Tumors - drug therapy; Purinergic P1 Receptor Agonists - pharmacology; Purinergic P1 Receptor Antagonists - pharmacology; Receptor, Adenosine A2A - biosynthesis; Receptor, Adenosine A2B - biosynthesis
Find related publications in this database (Keywords): Adenosine; A(2A) adenosine receptor; A(2B) adenosine receptor; Human neuroendocrine tumours; Cell proliferation; Chromogranin A