Importance of hepatic first-pass removal in metastasis of colon carcinoma cells

It might be thought that colon carcinoma tends to metastasize to the liver because tumor cells leaving the primary colon tumor pass initially through the liver. Therefore we elucidated the kinetics of tumor cells in the body in order to understand the effect of the location of the liver on hepatic metastasis, that is to examine the hepatic first-pass effect of tumor cells.

Based on a physiological kinetic model, we examined quantitatively the hepatic metastasis and hepatic distribution of KM12-H1X cells administered by different routes.

Both the number and incidence of colonies of hepatic metastasis were much greater after intrasplenic injection than after intravenous injection. The distribution of radioactivity to the liver after intrasplenic injection of [3H] thymidine-labeled cells was also much higher than that after intravenous injection. The number of colonies of hepatic metastasis correlated well with the area under the curve of the distributed amount of the tumor cells in the liver, regardless of the injection route; the correlation line was identical for each injection route.

These results suggest that the hepatic first-pass effect is an important factor for the hepatic metastasis and that the cumulative number of tumor cells distributed in the liver is a determining factor for the degree of metastasis. Mathematical analysis based on a physiological model also suggests that hepatic metastasis depends on hepatic first-pass trapping of tumor cells.