title: Osteonectin influences growth and invasion of pancreatic cancer cells.
abstract: OBJECTIVE
  We sought to examine the expression and functional role of osteonectin in primary and metastatic pancreatic ductal adenocarcinoma (PDAC).
  
  
  BACKGROUND
  The glycoprotein osteonectin plays a vital role in cell-matrix interactions and is involved in various biologic processes. Overexpression of osteonectin is present in malignant tumors and correlates with disease progression and poor prognosis.
  
  
  METHODS
  Expression of osteonectin was analyzed by quantitative polymerase chain reaction and immunohistochemistry in pancreatic tissues and by enzyme-linked immunosorbent assay in the serum of patients and donors. Recombinant osteonectin and specific antisense oligonucleotides were used to examine the effects of osteonectin on induction of target genes, and on proliferation and invasiveness of pancreatic cancer cells.
  
  
  RESULTS
  There was a 31-fold increase in osteonectin mRNA levels in PDAC and a 16-fold increase in chronic pancreatitis as compared with the normal pancreas (P < 0.01). By immunohistochemistry, faint immunoreactivity was detected in the normal pancreas. In contrast, strong staining of the cancer cells was observed in addition to extensive osteonectin immunoreactivity in surrounding fibroblasts and in the extracellular matrix. In metastatic tissues, strong immunoreactivity was observed in fibroblasts and in extracellular matrix surrounding metastatic cancer cells, whereas the signal was absent in most tumor cells. In vitro studies showed that osteonectin was able to inhibit cancer cell growth while promoting invasiveness of pancreatic tumor cells.
  
  
  CONCLUSIONS
  Osteonectin is markedly overexpressed in pancreatic cancer and has the potential to increase the invasiveness of pancreatic cancer cells.
authors.affiliation: Department of General Surgery, University of Heidelberg, Germany.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Guweidhi
authors.forename: Jörg
authors.initials: J
authors.lastname: Kleeff
authors.forename: Hassan
authors.initials: H
authors.lastname: Adwan
authors.forename: Nathalia A
authors.initials: NA
authors.lastname: Giese
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: Martin R
authors.initials: MR
authors.lastname: Berger
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000737:chemistry; D005260:Female; D005347:Fibroblasts / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D015676:Osteonectin / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D010195:Pancreatitis / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D016376:Oligonucleotides, Antisense; D015676:Osteonectin; D012333:RNA, Messenger; D011994:Recombinant Proteins