SELECTION FOR ENHANCED ADHESION TO MICROVESSEL ENDOTHELIAL-CELLS OR RESISTANCE TO INTERFERON-GAMMA MODULATES THE METASTATIC POTENTIAL OF MURINE RAW117 LARGE-CELL LYMPHOMA-CELLS

Poorly liver metastatic large-cell lymphoma RAW117-P cells were sequen tially selected in vitro for increased adhesion to murine hepatic sinu soidal endothelial cells. After three or four sequential selections, t he selected sublines showed increased rates of adhesion to target hepa tic microvessel endothelial cells and increased formation of experimen tal metastases in the liver. However, the endothelial cell adhesion-se lected RAW117 sublines were generally unstable and gradually lost thei r enhanced adhesive and metastatic properties during passage in cultur e. Highly metastatic, liver-selected RAW117-H10 large-cell lymphoma ce lls were more resistant to the cytostatic effects of interferon-gamma (IFN-gamma) than poorly metastatic unselected parental RAW117-P cells. When tested for their sensitivity to IFN-gamma, the endothelial cell adhesion variants were significantly more resistant than the unselecte d RAW117-P cells, but after a 72-h treatment with IFN-gamma, the in vi tro-selected cells lost their enhanced endothelial cell adhesion chara cteristics, their potential to colonize the liver, and their ability t o grow when injected at subcutaneous or intramuscular sites. In contra st, the metastatic potential of similarly treated RAW117-P cells was u naffected by IFN-gamma during a 72-h treatment. Sequential selection o f RAW117-P cells for increased resistance to IFN-gamma in vitro result ed in variant lines that were refractory to the growth-inhibiting effe cts of IFN-gamma, and these IFN-gamma-selected variants were also less adhesive to liver microvessel endothelial cells. The IFN-gamma-select ed variants also lost their experimental metastatic potentials complet ely anti their tumorigenicities at sites of subcutaneous or intramuscu lar injection. Cytofluorographic analysis indicated reduced cell surfa ce expression of H-2K(d) antigen and fibronectin receptor on the selec ted variant cells but no change ire cell surface mu heavy chain immuno globulin. The unselected and selected RAW117 lines had similar sensiti vities to natural killer (NK) cell-mediated cytolysis, indicating that the in vivo differences were probably not due to differences in NK ce ll-mediated cytolysis. The results suggest that selection for adhesion to organ microvessel endothelial cells or sequential exposure to cert ain cytokines can affect the adhesive, growth and metastatic propertie s of RAW117 cells without modifying their responses to NK cells.