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Time-dependent suppression of melanoma metastases and natural killer cell activation by interferon

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Summary

The effect of murine α/β interferon (IFN) on experimental metastasis was investigated using B16-F10 melanoma cells. Since the outcome of metastasis of blood-borne tumor cells is mainly determined within the first 24 h after i.v. inoculation of tumor cells, i.p. injection of IFN was focused on this critical early phase. The inhibition of pulmonary metastases by IFN was found to be maximal when given 3 h prior to tumor cell inoculation, while mice with 24-h and 12-h pretreatment and simultaneous IFN treatment also showed a reduction in metastases, but to a lesser extent. However, mice receiving IFN 2 h after tumor cell inoculation did not show any reduction. Tumor cells cultured for 24 h in IFN-containing medium showed no reduction in metastases. Administration of anti-asialo GMl prior to IFN treatment was found to eliminate the inhibitory effect of IFN 3 h pretreatment. However, natural killer (NK) cell activity in vitro measured at 3 h, 13 h and 24 h after IFN administration was enhanced to the same extent, not paralleling the inhibitory effect on pulmonary metastases. These data indicate that prepared host status against blood-borne tumor cells is established by IFN pretreatment, being maximal when injected several hours prior to tumor cell inoculation, and that this effect is substantially dependent on NK cell activity, though the implication of other factors is not excluded.

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References

  1. Brouty-Boyé D, Zetter BR (1980) Inhibition of cell motility by interferon. Science 208:516–518

    PubMed  Google Scholar 

  2. Djeu JY, Heinbaugh JA, Holden HT, Herberman RB (1979) Augmentation of mouse natural killer cell activity by interferon and interferon inducers. J Immunol 122: 175–181

    PubMed  Google Scholar 

  3. Fidler IJ (1970) Metastasis: Quantitative analysis of distribution and fate of tumor emboli labeled with 125I-5-iodo-2′-deoxyuridine. J Natl Cancer Inst 45:773–782

    PubMed  Google Scholar 

  4. Fidler IJ (1973) Selection of successive tumor lines for metastasis. Nat New Biol 242:148–149

    PubMed  Google Scholar 

  5. Fodstad Ø, Hansen CT, Cannon HB, Statham CN, Lichtenstein GR, Boyd MR (1984) Lack of correlation between natural killer activity and tumor growth control in nude mice with different immune defects. Cancer Res 44:4403–4408

    PubMed  Google Scholar 

  6. Glasgow LA, Kern ER (1981) Effect of interferon administration on pulmonary osteogenic sarcomas in an experimental murine model. J Natl Cancer Inst 67:207–210

    PubMed  Google Scholar 

  7. Habu S, Fukui H, Shimamura K, Kasai M, Nagai Y, Okumura K, Tamaoki N (1981) In vivo effect of anti-asialo GMl. I. Reduction of NK activity and enhancement of transplanted tumor growth in nude mice. J Immunol 127:34–38

    PubMed  Google Scholar 

  8. Hanna N (1982) Inhibition of experimental tumor metastasis by selective activation of natural killer cells. Cancer Res 42:1337–1342

    PubMed  Google Scholar 

  9. Hanna N, Burton RC (1981) Definitive evidence that natural killer (NK) cells inhibit experimental tumor metastasis in vivo. J Immunol 127:1754–1758

    PubMed  Google Scholar 

  10. Hanna N, Fidler IJ (1980) Role of natural killer cells in the destruction of circulating tumor emboli. J Natl Cancer Inst 65:801–809

    PubMed  Google Scholar 

  11. Imanishi J, Kita M, Sugino S, Oku T, Kishida T (1982) Elimination of polynucleotide-induced hyporeactivity in mice treated with interferon and antitumor therapy. J Interferon Res 2:65–74

    PubMed  Google Scholar 

  12. Imokawa G, Mishima Y (1982) Loss of melanogenic properties in tyrosinases induced by glycosylation inhibitors within malignant melanoma cells. Cancer Res 42:1994–2002

    PubMed  Google Scholar 

  13. Irimura T, Gonzales R, Nicolson GL (1981) Effects of tunicamycin on B16 metastatic melanoma cell surface glycoproteins and blood-borne arrest and survival properties. Cancer Res 41:3411–3418

    PubMed  Google Scholar 

  14. Lee SH, Chiu H, Rinderknecht W, Sabo W, Stebbing N (1983) Importance of treatment regimen of interferon as an antitumor agent. Cancer Res 43:4172–4175

    PubMed  Google Scholar 

  15. Matsuyama M (1979) Action of interferon on cell membrane of mouse lymphocytes. Exp Cell Res 124:253–259

    PubMed  Google Scholar 

  16. Mishima Y, Ueda M, Mojamdar M, Ichihashi M, Kita M, Kishida T (1983) Suppression of melanoma metastasis by interferon. In: Kishida T (ed) Interferons. Proceedings of the International Symposium on Interferons. Japan Convention Services Inc, Osaka, pp 62–67

    Google Scholar 

  17. Pfeffer LM, Wang E, Tamm I (1980) Interferon effects on microfilament organization, cellular fibronectin distribution, and cell motility in human fibroblasts. J Cell Biol 85:9–17

    Article  PubMed  Google Scholar 

  18. Poste G, Fidler IJ (1980) The pathogenesis of cancer metastasis. Nature (Lond) 283:139–146

    Google Scholar 

  19. Poste G, Nicolson GL (1980) Arrest and metastasis of blood-borne tumor cells are modified by fusion of plasma membrane vesicles from highly metastatic cells. Proc Natl Acad Sci USA 77:399–403

    PubMed  Google Scholar 

  20. Raz A, Ben-Ze'ev A (1983) Modulation of the metastatic capability in B16 melanoma by cell shape. Science 221:1307–1310

    PubMed  Google Scholar 

  21. Satomi H, Oku T, Kita M, Imanishi J, Kishida T (1983) Antimetastatic effect of interferon against murine osteogenic sarcoma. In: Kishida T (ed) Interferons. Proceedings of the International Symposium on Interferons. Japan Convention Services Inc, Osaka, pp 57–62

    Google Scholar 

  22. Schultz RM, Chirigos MA, Heine UI (1978) Functional and morphologic characteristics of interferon-treated macrophages. Cell Immunol 35:84–91

    PubMed  Google Scholar 

  23. Schulz RM, Papamatheakis JD, Chirigos MA (1977) Interferon: An inducer of macrophage activation by polyanions. Science 197:674–676

    PubMed  Google Scholar 

  24. Volk T, Geiger B, Raz A (1984) Motility and adhesive properties of high- and low-metastatic murine neoplastic cells. Cancer Res 44:811–824

    PubMed  Google Scholar 

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Ueda, M., Mishima, Y., Mojamdar, M. et al. Time-dependent suppression of melanoma metastases and natural killer cell activation by interferon. Arch Dermatol Res 278, 329–334 (1986). https://doi.org/10.1007/BF00407748

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  • DOI: https://doi.org/10.1007/BF00407748

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