Metastasis of mouse t-lymphoma-cells is controlled by the level of major histocompatibility complex class-i h-2d(k) antigens
Vandendriessche, Thierry Geldhof, A Bakkus, M Toussaintdemylle, D Brijs, L Thielemans, K Verschueren, H Debaetselier, P # ×
International Journal of Cancer vol:58 issue:2 pages:217-225
In vivo inoculation of a low metastatic BW 5147 derived T-cell lymphoma variant into syngeneic mice, had led to the generation of a highly metastatic variant. The shift towards a more metastatic phenotype is accompanied by an increase in major histocompatibility class I H-2D(k) antigen expression. This suggests that H-2D(k) antigens may control the metastatic potential of BW T lymphoma cells. Our present findings indicate that H-2D(k) expression is directly correlated with the metastatic potential of BW cells. We have confirmed such correlation by specifically altering the level of H-2D(k) expression by: 1) FACS analysis, 2) IFN-gamma treatment, 3) H-2D(k) gene transfection. Cells sorted for low H-2D(k) expression had a significantly reduced metastatic potential. Induction of H-2D(k) expression on these cells by either IFN-gamma treatment or H-2D(k) gene transfection concomitantly led to increased metastasis. We also assessed metastatic potential of BW cells in irradiated, immunocompromised recipients. Our results show that the immune system is implicated and we further tested which immune effectors are involved. In vivo depletion of natural killer (NK) and CD8(+) T-cells revealed that the difference in metastatic potential of the H-2D(k) variants relies upon on NK-dependent mechanism, whereas CD8(+) T-cells are not implicated. Our observations suggest that highly metastatic cells, expressing a high level of H-2D(k) antigens are more resistant to NK-cell-mediated cytotoxicity in vivo. We have confirmed our in vivo results by in vitro cytotoxicity assays using poly I:C induced NK and IL-2 activated LAK cells. We conclude that a NK-dependent mechanism accounts for the association between differential H-2D(k) antigen expression and metastasis. (C) 1994 Wiley-Liss, Inc.