title: Glucose-dependent insulinotropic polypeptide receptors in most gastroenteropancreatic and bronchial neuroendocrine tumors.
abstract: BACKGROUND
  Gastrointestinal peptide hormone receptors overexpressed in neuroendocrine tumors (NET), such as somatostatin or glucagon-like peptide-1 (GLP-1) receptors, are used for in vivo tumor targeting. Unfortunately, not all NET express these receptors sufficiently.
  
  
  OBJECTIVE
  Our aim was to evaluate in vitro the expression of another incretin receptor, glucose-dependent insulinotropic polypeptide (GIP) receptor, in human tumors and compare it with that in adjacent nonneoplastic tissues and also with somatostatin and GLP-1 receptor expression.
  
  
  METHODS
  GIP receptor protein expression was qualitatively and quantitatively investigated in 260 human tumors and in nonneoplastic human tissues with receptor autoradiography using [(125)I]GIP(1-30). Pharmacological competition experiments and mRNA analysis were performed to provide proof of specificity. Somatostatin receptor and GLP-1 receptor autoradiography were performed in adjacent sections.
  
  
  RESULTS
  GIP receptors are expressed in the majority of pancreatic, ileal, and bronchial NET. Importantly, most of the somatostatin receptor-negative NET and GLP-1 receptor-negative malignant insulinomas are GIP receptor positive. Conversely, the epithelial and stromal gastrointestinal tumors, including gastric, colonic, and hepatocellular carcinomas, cholangiocarcinomas, and gastrointestinal stromal tumors as well as lung adenocarcinomas are usually GIP receptor negative, except for 26% of pancreatic adenocarcinomas. Pancreatic islets, but not acini, are GIP receptor positive. The rank order of potencies for receptor binding and mRNA analysis by PCR reveal specific GIP receptors.
  
  
  CONCLUSIONS
  The numerous GIP receptors in gastroenteropancreatic and bronchial NET represent novel universal molecular targets for clinical applications, in particular for in vivo scintigraphy and targeted radiotherapy. These results may also be the basis for multiple targeting, with concomitant use of GIP, somatostatin, and GLP-1 analogs as radiotracers.
authors: Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, CH-3010 Berne, Switzerland.
authors: Beatrice
authors: B
authors: Waser
authors: Ruth
authors: R
authors: Rehmann
authors: Claire
authors: C
authors: Sanchez
authors: Daniel
authors: D
authors: Fourmy
authors: Jean Claude
authors: JC
authors: Reubi
mesh_terms: D001984:Bronchial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005749:Gastric Inhibitory Polypeptide / Q000493:pharmacokinetics; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009994:Osmolar Concentration; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000493:pharmacokinetics; D011964:Receptors, Gastrointestinal Hormone / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D018027:Receptors, Glucagon / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D011964:Receptors, Gastrointestinal Hormone; D018027:Receptors, Glucagon; C549099:gastric inhibitory polypeptide (1-30); D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor