ENHANCEMENT OF EXPERIMENTAL METASTASIS BY GAMMA-INTERFERON IN A MURINE ADENOCARCINOMA

This study was conducted to examine the effect of gamma-interferon (IF N-gamma) on experimental metastasis formation by murine colon 26 adeno carcinoma in BALB/c mice. We found that the number of experimental lun g metastases was increased after colon 26 cells were pretreated for 1 h with as little as 10IU/ml of IFN-gamma. 5-[I-125] iodo-2'-deoxyuridi ne-radiolabeled colon 26 cells pretreated with IFN-gamma remained at h igher level in the lung at 24 h after intravenous injection than when the cells were not pretreated. In vivo elimination of asialo GM(1)-pos itive cells increased the number of lung metastases and, in such mice, there was no longer a difference in metastatic ability between contro l and IFN-gamma-treated cells. Colon 26 cells were completely resistan t to lysis by isolated splenocytes. Splenocytes incubated in vitro wit h interleukin 2 exhibited moderate cytotoxicity against colon 26 cells , but there were no significant differences between control and IFN-ga mma-treated cells. Colon 26 cells pretreated with IFN-gamma demonstrat ed resistance to tumor necrosis factor alpha-mediated growth inhibitio n. The enhancement of metastases by IFN-gamma was dependent on de novo protein synthesis since the enhancement was abolished by cycloheximid e. Taken together, the data suggest that the metastatic ability of col on 26 cells pretreated with IFN-gamma is significantly higher due to t he resistance to asialo GM(1)-positive cells accompanied with de novo protein synthesis.