Natural killer cell activity is closely associated with a growth-inhibitory serum protein with protease-like activity.

A correlation between natural killer (NK) cell activity and growth inhibition (GI), as measured in an in vitro assay with B16 melanoma cells, mediated by a serum growth-inhibitory factor (GIF), among various strains of mice has been demonstrated. Beige mice (bg/bg), known to express low NK-activity, were also low in GIF activity and showed increased susceptibility to both B16 melanoma cells and another solid tumor (Lewis lung carcinoma) in vivo. In vivo treatment with various protease inhibitors that reduced NK-activity, also reduced growth inhibition mediated by GIF. Protease inhibitors that did not affect NK-activity did not affect GIF either. All of 4 B16 melanoma clones selected against GIF in vitro and resistant to GIF showed both resistance to NK-cells in vitro and increased growth potential in vivo. However, P-815, an NK-resistant cell line, was sensitive to GIF.