MODULATING THE METASTATIC POTENTIAL OF MURINE RAW117 LARGE-CELL LYMPHOMA-CELLS BY SELECTION FOR RESISTANCE TO INTERFERON-GAMMA

Highly metastatic, in vivo-selected cells of RAW117-H10 large-cell lym phoma have been shown to be more resistant than poorly metastatic pare ntal RAW117-P cells to the cytolytic and cytostatic activities of acti vated macrophages in co-culture experiments. Activated macrophages are known to produce soluble, cytostatic respiration-inhibiting factors, and such activities can be duplicated by interferon-gamma (IFN-gama) o r by combinations of IFN-gamma and Escherichia coli lipopolysaccharide (LPS). Highly metastatic RAW117-H10 cells are more resistant to the c ytostatic effects of IFN-gamma and LPS than poorly metastatic RAW117-P cells, and short-term (up to 72 hr) treatment with IFN-gamma and LPS does not change the metastatic potentials of RAW117 cells. We have stu died the effects of sequential selection of RAW117-P cells for increas ed resistance to IFN-gamma and LPS. After 7 to 13 sequential selection s, the resulting variant lines were completely refractory to the growt h-inhibitory effects of IFN-gamma and LPS and cross-tolerant to macrop hage-conditioned medium. The selected variants also completely lost th eir experimental metastatic potentials and their tumorigenicities afte r s.c. or i.m. injection. Cytofluorographic analysis indicated reduced cell-surface expression of H-2K(d) antigen and fibronectin receptor o n the variant cells but no change in surface mu heavy-chain immunoglob ulin. The IFN-gamma-selected lines were less adhesive to liver microva scular endothelial cells than the unselected RAW117 cell lines, but we re equally sensitive to NK cytolysis by spleen cells. Our results sugg est that exposure to certain cytokines can affect the growth and metas tatic potential of RAW117 cells and result in the selection of resista nt variants with altered biologic properties. (C) 1993 Wiley-Liss, Inc .