title: Laparoscopic staging of pancreatic tumors induces increased invasive capacity in vitro.
abstract: BACKGROUND
  Laparoscopy and laparoscopic ultrasound have a well-defined role in staging patients with pancreatic malignancy. The effect of the hypoxic pneumoperitoneum induction on tumor biology is unknown. The authors investigated whether an in vitro pneumoperitoneum augments the invasive capacity of pancreatic tumors and elucidate a mechanism by which this may occur.
  
  
  METHODS
  A pancreatic (PSN-1) adenocarcinoma cell line was exposed to an in vitro pneumoperitoneum (carbon dioxide (CO2) or helium) for a maximum of 2 h or left in normal growth conditions (control). Cells were nonenzymatically harvested and placed in invasion assays. These were performed over 72 h using Matrigel coated 8-mm Transwell filters and analyzed using MTS colorimetric assay. Gelatin zymography was employed to assess the level of matrix metalloproteases (MMP) 2 and 9 (gelatinase A and B) secretion. Expression of tissue inhibitor of metalloproteases 1 (TIMP-1) was assessed using ELISA (Biotrak). Inhibition of invasion assays was performed using a specific gelatinase inhibitor (MMPI; Calbiochem).
  
  
  RESULTS
  The invasive capacity of pancreatic tumour cells is augmented versus control in both helium (p <0.05) and CO2 (p <0.001) groups. Concomitant significant upregulation of the gelatinase activity was demonstrated with both insufflants (p <0.05; 0.001, respectively). Enhanced invasion was attenuated by the addition of a specific gelatinase inhibitor (p <0.05).
  
  
  CONCLUSIONS
  These results indicate the invasive capacity of pancreatic tumor cells is augmented by laparoscopic staging in vitro. This is in part mediated by increased gelatinase activity and may be attenuated by the addition of specific inhibitors.
authors.affiliation: Department of Surgical Oncology and Technology, Imperial College School of Medicine, St. Mary's Hospital, London, UK. p.ridgway@ic.ac.uk
authors.forename: P F
authors.initials: PF
authors.lastname: Ridgway
authors.forename: P
authors.initials: P
authors.lastname: Ziprin
authors.forename: T L
authors.initials: TL
authors.lastname: Jones
authors.forename: P A
authors.initials: PA
authors.lastname: Paraskeva
authors.forename: D H
authors.initials: DH
authors.lastname: Peck
authors.forename: A W
authors.initials: AW
authors.lastname: Darzl
mesh_terms: D000230:Adenocarcinoma / Q000145:classification / Q000201:enzymology / Q000473:pathology; D002245:Carbon Dioxide / Q000009:adverse effects; D006371:Helium / Q000009:adverse effects; D006801:Humans; D010535:Laparoscopy / Q000009:adverse effects / Q000379:methods; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000145:classification / Q000201:enzymology* / Q000473:pathology*; D011028:Pneumoperitoneum, Artificial / Q000009:adverse effects*; D019714:Tissue Inhibitor of Metalloproteinases / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D002245:Carbon Dioxide; D006371:Helium; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9