title: Pneumoperitoneum augmented tumor invasiveness is abolished by matrix metalloproteinase blockade.
abstract: BACKGROUND
  Certain surgical strategies, including Helium (He) and carbon dioxide (CO2) insufflation in laparoscopy, have been shown to induce a hypoxic environment. This may have a significant effect on the invasive capacity of tumor cells and may be a factor in the incidence of port-site metastases seen in patients following laparoscopic resection for malignancy.
  
  
  METHODS
  A colon adenocarcinoma cell line (SW1222) was exposed to an in vitro pneumoperitoneum of CO2 or He at 3 mmHg or left in normal growth conditions (control). After a 4-hour exposure to an in vitro pneumoperitoneum, the ability of the cells to invade through 8.0-microm Transwell filters coated with Matrigel was analyzed by colorimetric MTS assay and by direct staining of the filters. The effect of the addition of a known blocker of matrix metalloproteinases (MMPs), 1,10-phenanthroline (1,10-P), was investigated.
  
  
  RESULTS
  Cells exposed to an in vitro pneumoperitoneum demonstrate significantly increased invasive capacity compared to the control set, without loss of viability (He vs control, p <0.001; CO2 vs control, p <0.001). This augmented capacity is abolished by the addition of 1,10-P (p <0.01).
  
  
  CONCLUSIONS
  Exposure of a colonic adenocarcinoma cell line to either a CO2 or He pneumoperitoneum causes an increase in tumor cell invasiveness, which is abolished by the presence of a known inhibitor of MMPs. This suggests that MMPs have an important role in the metastatic potential of tumors exposed to a hypoxic operative environment.
authors.affiliation: Department of Surgical Oncology and Technology, Imperial College School of Medicine, St. Mary's Hospital, 10th Floor QEQM Wing, Praed Street, London W2 1NY, United Kingdom. p.ridgway@ic.ac.uk
authors.forename: P F
authors.initials: PF
authors.lastname: Ridgway
authors.forename: A
authors.initials: A
authors.lastname: Smith
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: Darzi
mesh_terms: D000230:Adenocarcinoma / Q000556:secondary*; D002245:Carbon Dioxide / Q000009:adverse effects; D002461:Cell Line, Transformed; D003110:Colonic Neoplasms / Q000556:secondary*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness; D009366:Neoplasm Seeding; D010618:Phenanthrolines / Q000494:pharmacology*; D011028:Pneumoperitoneum, Artificial / Q000009:adverse effects*; D011480:Protease Inhibitors / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D010618:Phenanthrolines; D011480:Protease Inhibitors; D002245:Carbon Dioxide; C025205:1,10-phenanthroline