Enhancement of port site metastasis by hyaluronic acid under CO2 pneumoperitoneum in a murine model

Background: The mechanism underlying the development and progression of port site metastasis after laparoscopic surgery for cancer is still not understood. Hyaluronic acid secreted from mesothelial cells is thought to be a key factor that causes adhesion between cancer cells and mesothelial cells. Using a murine model of carbon dioxide (CO2) pneumoperitoneum, we evaluated the effect of exogenous hyaluronic acid on port site metastasis. Methods: BALB/c mice were injected with 5 x 10(6) human gastric carcinoma (MKN45) cells and divided into four groups treated with or without hyaluronic acid and with or without pneumoperitoneum. Three weeks later, the frequency and weight of port site metastases were determined. The effects of hyaluronic acid on tumorigenicity and tumor growth were examined in mice subcutaneously injected with MKN45 cells. Results: Port site metastasis occurred significantly less frequently in the pneumoperitoneum-only group than in the pneumoperitoneum-with-hyaluronic-acid group (75% vs 100%, p < 0.05). The port site metastatic tumor weighed significantly less in the control group (anesthesia only) than in the hyaluronic acid group (89 +/- 17 vs 288 +/- 35 mg, p < 0.05); it also weighed less in the pneumoperitoneum-only group than in the pneumoperitoneum-with-hyaluronic-acid group (87 +/- 24 vs 298 +/- 51 mg, p < 0.05). The frequency and weight of tumors in the subcutaneous tissue were not significantly different between groups with or without hyaluronic acid injection (95% vs 90%, 331 +/- 128 vs 322 +/- 115 mg). Conclusions: Under CO2 pneumoperitoneum, exogenous hyaluronic acid increased the frequency and weight of port site metastasis in a murine model. Hyaluronic acid secreted from mesothelial cells may be associated with the formation of port site metastasis after laparoscopic surgery for cancer under pneumoperitoneum.