Modulation of colon-derived experimental hepatic metastasis by murine nonparenchymal liver cells.
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-GM1 decreased the lifespan of MCA-38 tumor bearing mice suggesting that asialo-GM1 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.
Cohen
S A
SA
Department of Medicine, VA Medical Center, Buffalo, NY 14215.
Goldrosen
M H
MH
D000230:Adenocarcinoma / Q000276:immunology / Q000556:secondary / Q000628:therapy; D000818:Animals; D003110:Colonic Neoplasms; D003602:Cytotoxicity, Immunologic; D005677:G(M1) Ganglioside; D006028:Glycosphingolipids / Q000037:antagonists & inhibitors; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000556:secondary* / Q000628:therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000494:pharmacology
D006028:Glycosphingolipids; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D011070:Poly I-C