Modulation of colon-Derived Experimental Hepatic Metastasis by murine Nonfarenchymal liver Cells

Abstract

Although numerous animal tumor models have been used to study colon carcinoma, few display hepatic metastasis. C57B1/6Ros mice inoculated with liver-derived murine colon adenocarcinoma MCA-38 in the ileocolic vein develop distinct hepatic foci within 21 days and survive an average of 35 days. Furthermore, ¹¹¹In-labeled LD-MCA-38 tumor cells were rapidly taken up by the liver within 60 min and 73% of the label remained in the liver after 24 h. Isolated nonparenchymal liver cells from untreated mice displayed little cytotoxicity against freshly excised ⁵¹Cr-labeled MCA-38 cells but did inhibit tumor growth in vitro as measured by inhibition of ³H-thymidine incorporation. Treatment with anti-asialo-G_M1 decreased the lifespan of MCA-38 tumor bearing mice suggesting that asialo-G_M1 positive cells in the liver may inhibit tumor growth in vivo. Nonparenchymal liver cells from mice treated with polyinosinic-polycytidylic acid showed augmented cytotoxic and cytostatic activity against LD-MCA-38 tumor cells in vitro. Polyinosinic-polycytidylic acid treatment also significantly increased the lifespan of MCA-38 tumor bearing mice. In conclusion, the host defense system of the liver can be modulated to enhance or inhibit colon-derived experimental hepatic metastasis.