title: The neurotrophic factor artemin promotes pancreatic cancer invasion.
abstract: OBJECTIVE
  To analyze the role of Artemin in pancreatic ductal adenocarcinoma (PDAC) in terms of expression, influence on cancer cell behavior, and pain correlation.
  
  
  BACKGROUND
  PDAC is characterized by prominent local nerve alterations and perineural invasion, which frequently affects the extrapancreatic nerve plexus, causing severe pain and precluding curative resection. Artemin, a neurotrophic protein controlling growth, regeneration, and survival of neurons was analyzed to highlight the neuro-cancer interactions in PDAC.
  
  
  METHODS
  Artemin and its receptors (GFRalpha3/RET) were studied in PDAC tissues and normal pancreas by Western blot analysis and immunohistochemistry. RNA expression was analyzed in pancreatic tissues (normal, cancer) and pancreatic cancer cell lines by QRT-PCR. To evaluate whether Artemin influences cancer cell proliferation and invasion, MTT-growth and Matrigel-invasion assays were used. In addition, the tissue expression of Artemin was correlated with pain in PDAC.
  
  
  RESULTS
  Artemin and GFRalpha3/RET were both detected at enhanced levels in PDAC compared with normal pancreas, localizing predominantly in hypertrophic nerves and arterial walls, as well as in cancer cells of primary and metastatic lesions. The levels of Artemin and GFRalpha3 did not correlate with pain in PDAC patients. However, Artemin promoted pancreatic cancer cell invasion up to 5-fold, without affecting cancer cell proliferation.
  
  
  CONCLUSIONS
  Artemin expression was not associated with pain in PDAC. However by increasing cancer cell invasion, Artemin seems to influence neural invasion and thereby contribute to cancer cell spreading along pancreatic nerves.
authors.affiliation: Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Güralp O
authors.initials: GO
authors.lastname: Ceyhan
authors.forename: Nathalia A
authors.initials: NA
authors.lastname: Giese
authors.forename: Mert
authors.initials: M
authors.lastname: Erkan
authors.forename: Annika G
authors.initials: AG
authors.lastname: Kerscher
authors.forename: Moritz N
authors.initials: MN
authors.lastname: Wente
authors.forename: Thomas
authors.initials: T
authors.lastname: Giese
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000503:physiopathology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004396:Coloring Agents; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000502:physiology; D006801:Humans; D006984:Hypertrophy; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D009414:Nerve Growth Factors / Q000032:analysis / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000502:physiology*; D009474:Neurons / Q000473:pathology; D010146:Pain / Q000503:physiopathology; D010179:Pancreas / Q000294:innervation / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: C490886:ARTN protein, human; D004396:Coloring Agents; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue