title: Distribution of CCK1 and CCK2 receptors in normal and diseased human pancreatic tissue.
abstract: OBJECTIVE
  The localization and functional role of cholecystokinin (CCK) receptor proteins in normal and diseased human pancreas, particularly in ductal pancreatic carcinomas, remain unclear.
  
  
  METHODS
  Tissue samples of normal human pancreas, chronic pancreatitis, and ductal pancreatic carcinomas were investigated under carefully controlled conditions for expression of CCK1 and CCK2 receptor messenger RNA (mRNA) and proteins using in situ hybridization and in vitro CCK receptor autoradiography by means of subtype-selective analogues. Synaptophysin immunohistochemistry was used concomitantly for optimal identification of islets, nerves, and tumor areas with neuroendocrine features.
  
  
  RESULTS
  CCK2 receptor mRNA and proteins were found abundantly in human pancreatic islets in normal pancreas and chronic pancreatitis. CCK1 receptor proteins were found occasionally in small-sized pancreatic nerves, whereas acini expressed a low density of CCK2 receptors in a few cases of chronic pancreatitis. Ductal pancreatic carcinomas rarely expressed CCK receptors; a few receptor-positive tumors, often characterized by neuroendocrine differentiation, expressed the CCK2 receptor at the mRNA or protein level. However, the main source of CCK receptors in the pancreatic tumor samples consisted of CCK2-expressing islets and/or CCK1-expressing nerves rather than neoplastic tissue.
  
  
  CONCLUSIONS
  These data indicate that the presence of CCK receptors in human ductal pancreatic tumor samples is mainly due to CCK2 expression in residual pancreatic islets and CCK1 in pancreatic nerves. Pancreatic acini and ductal pancreatic tumor cells very rarely express CCK2 receptors. These observations suggest that CCK analogues may not be of clinical use to target most of these cancers.
authors.affiliation: Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Switzerland. reubi@pathology.unibe.ch
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Reubi
authors.forename: Beatrice
authors.initials: B
authors.lastname: Waser
authors.forename: Mathias
authors.initials: M
authors.lastname: Gugger
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
authors.forename: Jörg
authors.initials: J
authors.lastname: Kleeff
authors.forename: Hany
authors.initials: H
authors.lastname: Kayed
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.forename: Jean A
authors.initials: JA
authors.lastname: Laissue
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001345:Autoradiography; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D017615:Enteric Nervous System / Q000737:chemistry; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000737:chemistry / Q000294:innervation / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D010195:Pancreatitis / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000032:analysis / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin