Suppression of pulmonary tumour metastasis in mice by recombinant human interleukin-2: role of asialo GM1-positive cells

Abstract

Recombinant human interleukin-2 (rIL-2) suppressed metastatic tumour colony formation in the lungs of C57BL/6 mice bearing Lewis lung carcinoma (3LL). In tumour-bearing mice given rIL-2, non-specific killer cells that were cytotoxic not only against natural killer-sensitive YAC-1 cells but also against 3LL cells in an in vitro 51Cr-release assay were concomitantly induced as tumour metastasis was suppressed. These non-specific killer cells were mostly removed by treatment with anti-Thy 1.2 or anti-asialo GM1 antibody plus complement (C) in vitro but not with anti-Lyt 1.2 or anti-Lyt 2.2 plus C, indicating that they were positive for Thy 1 and asialo GM1 but not for Lyt 1 and Lyt 2. In order to explore the mechanism by which rIL-2 suppressed tumour metastasis, we examined the clearance of intravenously injected 51Cr-labelled 3LL cells in the lungs of mice given rIL-2. The rate of tumour cell clearance was increased. This enhanced clearance was almost completely removed by injecting anti-asialo GM1 antibody. In addition, the injection of anti-asialo GM1 antibody also depleted most of the non-specific killer cells induced by administering rIL-2. These results indicate that asialo GM1-positive cells are not only cytotoxic in vitro but also play a critical role in the clearance of 3LL cells in the lungs in vivo. Our results indicate that asialo GM1-positive cells play an important role as anti-metastatic effector cells in suppressing the metastasis of 3LL cells in mice given rIL-2.