title: Expression of a prometastatic splice variant of osteopontin, OPNC, in human pancreatic ductal adenocarcinoma.
abstract: BACKGROUND
  Osteopontin (OPN) is a secreted phosphoprotein that confers on cancer cells a migratory phenotype. We demonstrated recently that nicotine, a major risk factor in pancreatic ductal adenocarcinoma (PDA), increases OPN expression in PDA cells. An OPN splice variant, OPNc, supports anchorage independence and maybe the most potent OPN isoform to convey metastatic behavior. In this study, we tested the effect of nicotine on OPNc expression and analyzed the correlation between total OPN/OPNc levels and patients' smoking history.
  
  
  METHODS
  Real-time polymerase chain reaction and ultraviolet light illumination of ethidium-bromide staining were used to examine the mRNA expression in tissue and in PDA cells treated with or without nicotine (3-300 nmol/L). OPN and OPNc were localized by immunohistochemistry, and an enzyme-linked immunosorbent assay was used to analyze OPN serum levels.
  
  
  RESULTS
  Nicotine treatment of PDA cells selectively induced de novo expression of OPNc. OPNc was found in 87% of invasive PDA lesions, of which 73% were found in smokers. The levels of OPNc correlated well with higher expression levels of total OPN in the tissue and serum from patients with invasive PDA.
  
  
  CONCLUSIONS
  Our data suggest that smoking and nicotine may contribute to PDA metastatic potential through promoting OPNc expression. Although the direct role of OPNc in PDA progression is not defined, OPNc may have value as a diagnostic and prognostic marker, especially in invasive PDA.
authors.affiliation: Department of Surgery, Jefferson Pancreatic, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sullivan
authors.forename: Laurel
authors.initials: L
authors.lastname: Blair
authors.forename: Amer
authors.initials: A
authors.lastname: Alnajar
authors.forename: Tamer
authors.initials: T
authors.lastname: Aziz
authors.forename: Chee Yuan
authors.initials: CY
authors.lastname: Ng
authors.forename: Galina
authors.initials: G
authors.lastname: Chipitsyna
authors.forename: Qiaoke
authors.initials: Q
authors.lastname: Gong
authors.forename: Agnes
authors.initials: A
authors.lastname: Witkiewicz
authors.forename: Georg F
authors.initials: GF
authors.lastname: Weber
authors.forename: David T
authors.initials: DT
authors.lastname: Denhardt
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Yeo
authors.forename: Hwyda A
authors.initials: HA
authors.lastname: Arafat
mesh_terms: D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000556:secondary*; D045744:Cell Line, Tumor; D034201:Computers, Handheld; D006801:Humans; D007150:Immunohistochemistry; D009538:Nicotine / Q000494:pharmacology; D053495:Osteopontin / Q000235:genetics* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012907:Smoking; D014407:Tumor Cells, Cultured
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D053495:Osteopontin; D009538:Nicotine