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).

Conclusion: 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.