title: Plasma Shh levels reduced in pancreatic cancer patients.
abstract: OBJECTIVE
  Normally, sonic hedgehog (Shh) is expressed in the pancreas during fetal development and transiently after tissue injury. Although pancreatic cancers express Shh, it is not known if the protein is secreted into the blood and whether its plasma levels change with pancreatic transformation. The goal of this study was to develop an enzyme-linked immunosorbent assay to detect human Shh in blood and determine its levels in subjects with and without pancreatic cancer.
  
  
  METHODS
  A human Shh enzyme-linked immunosorbent assay was developed, and plasma Shh levels were measured in blood samples from healthy subjects and patients with pancreatitis or pancreatic cancer. The biological activity of plasma Shh was tested using NIH-3T3 cells.
  
  
  RESULTS
  The mean levels of Shh in human blood were lower in patients with pancreatitis and pancreatic cancer than in healthy subjects. Hematopoietic cells did not express Shh, suggesting that Shh is secreted into the bloodstream. Plasma fractions enriched with Shh did not induce Gli-1 messenger RNA, suggesting that the protein was not biologically active.
  
  
  CONCLUSIONS
  Shh is secreted from tissues and organs into the circulation, but its activity is blocked by plasma proteins. Reduced plasma levels were found in pancreatic cancer patients, but alone were not sufficient to predict pancreatic cancer.
authors.affiliation: Department of Internal Medicine-Gastroenterology, University of Michigan, Ann Arbor, MI 48109-2200, USA
authors.forename: Mohamad
authors.initials: M
authors.lastname: El-Zaatari
authors.forename: Stephanie
authors.initials: S
authors.lastname: Daignault
authors.forename: Art
authors.initials: A
authors.lastname: Tessier
authors.forename: Gail
authors.initials: G
authors.lastname: Kelsey
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Travnikar
authors.forename: Esperanza F
authors.initials: EF
authors.lastname: Cantu
authors.forename: Jamie
authors.initials: J
authors.lastname: Lee
authors.forename: Caitlyn M
authors.initials: CM
authors.lastname: Plonka
authors.forename: Diane M
authors.initials: DM
authors.lastname: Simeone
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Anderson
authors.forename: Juanita L
authors.initials: JL
authors.lastname: Merchant
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D053823:Hedgehog Proteins / Q000097:blood* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008297:Male; D051379:Mice; D008875:Middle Aged; D041681:NIH 3T3 Cells; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000097:blood*; D010195:Pancreatitis / Q000097:blood; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D000071676:Zinc Finger Protein GLI1
chemical_list: D001798:Blood Proteins; C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; C509239:SHH protein, human; D000071676:Zinc Finger Protein GLI1