title: Trefoil factor family peptides in normal and diseased human pancreas.
abstract: OBJECTIVE
  Trefoil factor family (TFF) peptides promote wound healing in the gut. Recent evidence has suggested that TFF3 may be a pancreatic mitogen, an unusual role for TFF peptides. We sought to clarify human pancreatic TFF and mucin expression and performed in vitro experiments to see how pancreatic cell lines respond to TFF3 in particular.
  
  
  METHODS
  Samples of normal and diseased pancreas (chronic pancreatitis, pancreatic intraepithelial neoplasia, neuroendocrine tumors, and pancreatic ductal adenocarcinoma [PDAC]) were studied by immunohistochemistry and in situ hybridization. Pancreatic cell lines were challenged with TFF2 and TFF3 in wound and migration assays.
  
  
  RESULTS
  In normal islets, colocalization of insulin or glucagon with TFF3 was common. All TFF messenger RNAs were seen in ductal epithelium. Adenocarcinomas expressed all TFF messenger RNAs. Normal ducts were mucin free; MUC5AC was strongest in pancreatic intraepithelial neoplasia and chronic pancreatitis but was reduced in PDAC. TFF2 induced Panc-1 migration and accelerated wound closure in Capan-2 and COLO-357. Double immunohistochemistry for insulin or TFF3 and Ki67 colabeled only very rare islet cells. TFF3-positive PDAC ducts showed some Ki67 colocalization.
  
  
  CONCLUSIONS
  No correlation between TFF3 or insulin and Ki67 was seen without ductal hyperplasia. TFF2 may assist pancreatic tumor cell movement, but TFF3 may not be a pancreatic mitogen.
authors.affiliation: Histopathology Laboratory, Cancer Research UK, London Research Institute, London, UK.
authors.forename: Naomi J
authors.initials: NJ
authors.lastname: Guppy
authors.forename: Mona E
authors.initials: ME
authors.lastname: El-Bahrawy
authors.forename: Hemant M
authors.initials: HM
authors.lastname: Kocher
authors.forename: Kornelia
authors.initials: K
authors.lastname: Fritsch
authors.forename: Yassar A
authors.initials: YA
authors.lastname: Qureshi
authors.forename: Richard
authors.initials: R
authors.lastname: Poulsom
authors.forename: Rosemary E
authors.initials: RE
authors.lastname: Jeffery
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Wright
authors.forename: William R
authors.initials: WR
authors.lastname: Otto
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Alison
mesh_terms: D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007328:Insulin / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D055271:Mucin 5AC / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology; D010182:Pancreatic Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3
chemical_list: D007328:Insulin; D019394:Ki-67 Antigen; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D010455:Peptides; D012333:RNA, Messenger; C000604007:TFF2 protein, human; C082495:TFF3 protein, human; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D005934:Glucagon