DETERMINANTS OF DIFFERENTIAL LIVER-COLONIZING POTENTIAL OF VARIANTS OF THE MCA-38 MURINE COLON-CANCER CELL-LINE

We investigated factors that might contribute to the differing liver t umor colonizing potentials of MCA-38 colonic cancer cell line variants injected into the ileocolic veins of C57Bl/6J mice. Non-colonizing (M CA-38 CD) cells were sensitive to lysis by hepatic ntural killer (NK) cells in vitro (Cr-51-release assay) and cells with high liver-coloniz ing potential (MCA-38 LD) were resistant. Following abrogation of NK a ctivity by treatment with anti-asialoG(M1), liver-colonizing ability o f LD cells but not CD cells was enhanced. MCA-38 CD cells were, howeve r, capable of initial liver colonization after ileocolic vein injectio n. Differing patterns of membrane sialylation may have contributed to the contrasting hepatic tumorigenicities of LD and CD cells; beta-gala ctoside alpha 2,6-sialyltransferase mRNA levels and activity were simi lar to four-fold higher in LD than CD cells and qualitative and quanti tative differences existed between their ganglioside profiles. In the MCA-38 model outlined, tumor cell susceptibility or resistance to NK l ysis was a relatively unimportant determinant of liver-colonizing pote ntial.