Bovine Lactoferrin and LactoferricinTM Inhibit Tumor Metastasis in Mice
The effect of a bovine milk protein, lactoferrin (bLf), and a pepsin-generated peptide of bLf, lactoferricin (Lfcin-B), on inhibition of tumor metastasis produced by highly metastatic murine tumor cells, B16-BL6 melanoma and L5178Y-ML25 lymphoma cells, was examined in experimental and spontaneous metastasis models using syngeneic mice. The subcutaneous (s.c.) administration of bovine apo-lactoferrin (apo-bLf) and Lfcin-B 1 day after tumor inoculation significantly inhibited liver and spleen metastasis of L5178Y-ML25 cells and lung metastasis of B16-BL6 cells, whereas human apo-lactoferrin (apo-hLf) and bovine holo-lactoferrin (holo-Lf) at the dose of 1 mg/mouse did not. Furthermore, both apobLf and Lfcin-B, but not apo-hLf and holo-bLf, inhibited the number of tumor-induced blood vessels and suppressed tumor growth on day 8 after tumor inoculations in an in vivo model. However, in a long-term analysis of tumor growth for up to 21 days after tumor inoculation, single administration of apo-bLf significantly suppressed the growth of B 16-BL6 cells throughout the examination period, but Lfcin-B showed inhibitory activity only during the early period (8 days). In spontaneous metastasis model, multiple administration of both apo-bLf and Lfcin-B significantly inhibited lung metastasis of B16-BL6 cells, however it was only apo-bLf that exhibited the inhibitory effect of tumor growth at the time of primary tumor amputation (on day 21) after tumor inoculation. The results suggest that apo-bLf and Lfcin-B inhibit tumor metastasis through different mechanisms, and that the inhibitory activity of bLf on tumor metastasis maybe related to the property of iron (Fe3+)-saturation.
KeywordsLung Metastasis Tumor Metastasis Suppress Tumor Growth Tumor Inoculation Antimetastatic Effect
Unable to display preview. Download preview PDF.
- 1.Reiter. B. In “ Development in Dairy Chemistry-3, Lactose and Minor Constituents, ed. P.F. Fox, London, pp. 281–336 (1985). Elsevier Applied Sci. Pub.Google Scholar
- 6.Lomita, M.. Bellamy, W., Takase, M., Yamauchi, K. Wakabayashi, H. and Kawase, K. J. Dairy Sei., 74, 4137-ßl42(1992).Google Scholar
- 7.Bellamy, W., Takase, M.. Yamauchi, K., Wakabayashi, H., Kwase, K. and Tomita, M. Biochim. Biophys. Acta, 1121, 134–136 (1992).Google Scholar
- 8.Bezault. J., Bhimani, R., Wiprovnick, J. and Furmanski, P. Cancer Res., 54, 2310–2312 (1994).Google Scholar
- 9.Pierce, A., Colavizza, D., Benaissa, M., Macs, P., Tartar, A., Montreuil, J. and Spik, G. Fur. J. Biochem., 196, 177 184 (1991).Google Scholar
- 10.Shan, H., Kim, A. and Golub, H. J. Leukocyte Biol., 51, 343–349 (1992).Google Scholar
- 11.Yoo, Y. C., Saiki, I.. Sato, K. and Azuma, 1. Vaccine, 12, 175–180 (1994).Google Scholar
- 13.Shimazaki. K., Kawano, N. and Yoo, Y. C. Comp. Biochem. Physiol., 98, 417–422 (1991).Google Scholar
- 14.Yoo. Y. C.. Saiki. I., Sato, K. and Azuma, I. Vaccine, 10, 792–797 (1992).Google Scholar
- 15.Saiki, I., Sato, K., Yoo, Y. C., Murata, J., Yoncda, J., Kiso, M.. Hasegawa, M. and Azuma, 1. Int..1. Cancer, 51, 641–045 (1992).Google Scholar
- 17.Anderson, B. F., Baker, I1. M., Norris, G. E., Rice, D. W. and Baker, E. N. J. Mol. Biol., 209. 711–734 (1989).Google Scholar