Adenosine A 2A and A 2B receptor expression in neuroendocrine tumours: Potential targets for therapy

A. Kalhan, B. Gharibi, M. Vazquez, B. Jasani, J. Neal, M. Kidd, I. M. Modlin, R. Pfragner, D. A. Rees, J. Ham

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

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 2AR 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.

Original languageEnglish
Pages (from-to)265-274
Number of pages10
JournalPurinergic Signalling
Volume8
Issue number2
DOIs
Publication statusPublished - Jun 2012

Keywords

  • A adenosine receptor
  • A adenosine receptor
  • Adenosine
  • Cell proliferation
  • Chromogranin A
  • Human neuroendocrine tumours

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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