Indomethacin inhibits kidney metastasis in bomirski melanoma-bearing hamsters, and modulates natural killer cytotoxic activity of tumor hosts in vivo and in vitro.

Natural killer (NK) cells are thought to play an important role in the control of metastatic dissemination. Therefore, stimulation of cytotoxic activity of NK cells against neoplastic cells could be preventive for metastatic spread. Bomirski amelanotic (Ab) melanoma of Syrian hamster is a transplantable tumor metastasizing preferably to the kidneys. During growth of the melanoma a significant depression of cytotoxic activity of NK cells of tumor hosts is observed. Treatment of melanoma-bearing hamsters with indomethacin provided in drinking water resulted in the increase of NK cytotoxic activity of blood cells and in the lower occurrence of kidney metastasis. Spleen cells obtained from healthy and melanoma-bearing hamsters were cultured in vitro with agents influencing NK activity. We found an augmentative effect of human interleukin 2 (IL2) and human tumor necrosis factor (TNF). We also observed the synergistic effect of IL2/TNF combination, which was present in both groups of animals. The stimulatory effects of cytokines could be potentiated by the additional supplementation of cultures with indomethacin. Similar experiments were performed on spleen cells isolated from the healthy and tumor-bearing animals treated in vivo with indomethacin. Also, in this group of hamsters in vitro stimulation of NK cell activity by the cytokines was effective. The studies presented may give insight into the pathogenesis of immune abnormalities seen in advanced stages of progression of Ab melanoma, and can provide an experimental basis for immunomodulation in this tumor model of spontaneous metastasis.