The plasminogen activator inhibitor system in colon cancer cell lines is influenced by the CO2 pneumoperitoneum

Abstract

PurposeLaparoscopic surgery in the treatment of colon carcinoma causes pH value alterations as well as changes in fibrinolytic activity. This results in enhanced proliferation of colon carcinoma cells in vitro and also in enhanced growth of liver metastasis when compared to isobaric (gasless) laparoscopy in vivo. So far, the direct influence of CO2 pneumoperitoneum on the invasiveness and metastatic capabilities of colon cancer cells remains unclear. We therefore evaluated transcripts of the uPA system.MethodsThe influence of CO2 pneumoperitoneum on the gene expression of plasminogen activator inhibitor-1 (PAI-1), urokinase-type plasminogen activator (uPA), and tissue-type plasminogen activator (tPA) was investigated in colon carcinoma cell lines (HT116, SW48, and WiDr) and mesothelial cells employing a pneumoperitoneum chamber in vitro. Quantitative gene expression data were collected using real-time RT-PCR and statistical analysis was performed by means of analysis of variance and Bonferroni correction.ResultsThe expression of uPA and PAI-1 was increased in colon carcinoma cell lines when cultivated at pH 6.1, a value corresponding to intraabdominal pH values during CO2 insufflation. Elevated PAI-1 mRNA levels were also observed when CO2 was simultaneously applied with a pressure of 10 mmHg. In contrast, there were no significant changes in mesothelial cells in the investigated parameter.ConclusionThe conditions of CO2 pneumoperitoneum cause changes in the expression of genes controlling the fibrinolytic activity. The increase of PAI-1 and uPA can contribute to the enhancement of metastasis and invasive potential of tumour cells. Therefore, changes in the conditions of laparoscopy may well optimise laparoscopic therapy in colon cancer.