TNF PROMOTES METASTASIS BY IMPAIRING NATURAL-KILLER-CELL ACTIVITY

Inflammatory mediators such as tumor necrosis factor (TNF) and interle ukin-1 enhance tumor colony formation in different models of experimen tal and spontaneous metastasis. The involvement of the natural killer (NK) cell system in this process was investigated. Tumor necrosis fact or does not appear to act directly on tumor cells by reducing their su sceptibility to the cytotoxic action of NK cells but rather impairs NK activity in tumor-bearing mice. Such impairment of the natural killer system might be one means by which TNF supports tumor colony formatio n. Even though the metastasis-enhancing effect of TNF remained detecta ble in mice which have a greatly reduced NK cell cytotoxic activity du e to a defect in the bg locus, normal mice which were depleted of NK c ells by antibody treatment did not show enhanced metastasis after TNF injection. Therefore, the TNF-enhanced metastasis can only be seen as long as some NK cell function is operating in the animals. (C) 1996 Wi ley-Liss, Inc.