Abstract
We have previously reported that abdominal irradiation of mice inhibited lung metastases of a weakly immunogenic fibrosarcoma, and that transmigration after the irradiation ofEnterobacter cloacae into mesenteric lymph nodes coincided with this phenomenon. In this paper, we show thatEscherichia coli as well asE. cloacae reduce the number of metastatic lung colonies when these bacteria were intravenously injected into mice prior to the tumour cell challenge. The inhibition was caused not only by the administration of living bacteria but also by that of killed bacteria. Bacterial lipopolysaccharide (LPS), a component of membrane, replaced at least in part the effect of whole bacteria. Transfer of spleen cells from LPS-treated mice into intact recipients prominently inhibited metastatic development in the recipient mice. ‘Cross transfer’ between LPS high responders and LPS low responders suggested an indirect activity of transferred spleen cells. The antimetastatic activity of LPS depended on the tumour cell type; metastasis of fibrosarcomas was extensively inhibited by LPS irrespective of tumour immunogenicity while that of adenocarcinomas was only slightly inhibited. These results suggest that non-immunological mechanisms are involved in the antimetastatic activity of LPS.
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Peters, L. J., 1975, Enhancement of syngeneic murine tumor transplantability by whole body irradiation—a non-immunological phenomenon.British Journal of Cancer,31, 293–300.
Ando, K., Hunter, N., andPeters, L. J., 1980, Inhibition of artificial lung metastases in mice by pre-irradiation of abdomen.British Journal of Cancer,41, 250–258.
Ando, K., Peters, L. J., Hunter, N., Jinnouchi, K., andMatsumoto, T., 1983, Inhibition of artificial and spontaneous metastases by preirradiation of abdomen—II.British Journal of Cancer,47, 73–79.
Matsumoto, T., Ando, K., andKoike, S., 1988, Significance of bacterial flora in abdominal irradiation-induced inhibition of lung metastases.Cancer Research,48, 3031–3034.
Maejima, K., Maejima, F., andTaijima, Y., 1968, Viable count of various bacteria in the digestive tract of mice. IV. Enumeration of organisms in the stomach and different regions of the intestine.Experimental Animals,17, 142–149.
McIntire, F. C., Sievert, H. W., Barlow, G. H., Finley, R. A., andLee, A. Y., 1976, Chemical, physical, and biological properties of a lipopolysaccharide fromEscherichia coli K-235.Biochemistry,6, 2363.
Tomita, T., Iwashita, S., andKanegasaki, S., 1976, Role of cell surface mobility of bacteriophage infection: translocation ofSalmonella phages of membrane adhesions.Biochemical and Biophysical Research Communications,73, 807–813.
Vincent, J. G., Veomett, R. C., andRiley, R. F., 1955, Relation of the indigenous flora of the small intestine of the rat to post-irradiation bacteremia.Journal of Bacteriology,69, 38–44.
Trier, J. S., andBrowning, T. H., 1966, Morphologic response of the mucosa of human small intestine to X-ray exposure.Journal of Clinical Investigation,45, 194–204.
Rosoff, C. B., 1963, The role of intestinal bacteria in the recovery from whole body irradiation.Journal of Experimental Medicine,118, 935–943.
Mastromarino, A., andWilson, R., 1976, Antibiotic radioprotection of mice exposed to supralethal whole-body irradiation independent of antibacterial activity.Radiation Research,68, 329–338.
Quastler, H., 1956, The nature of intestinal radiation death.Radiation Research,4, 303–320.
Wilson, B. R., 1963, Survival studies of whole-body X-irradiated germfree (axenic) mice.Radiation Research,20, 477–483.
Anderson, R. E., Howarth, J. L., andStone, R. S., 1968, Acute response of germfree and conventional mice to ionizing radiation.Archives of Pathology and Laboratory Medicine,86, 676–680.
Klainer, A. S., Gorbach, S., andWeinstein, L., 1967, Study of intestinal microflora. VI. Effect of X-irradiation on the fecal microflora of the rat.Journal of Bacteriology,94, 378–382.
Meyrick, B., andBrigham, K. L., 1983, Acute effects ofE. coli endotoxin on the pulmonary microcirculation of anesthetized sheep.Laboratory Investigation,48, 458–470.
Berendt, M. J., North, R. J., andKirstein, D. P., 1978, The immunological basis of endotoxin-induced tumor regression.Journal of Experimental Medicine,148, 1550–1559.
McGhee, J. R., Farrar, J. J., Michalek, S. M., Mergenhagen, S. E., andRosenstreich, D. L., 1979, Cellular requirements for lipopolysaccharide adjuvanticity. A role for both T lymphocytes and macrophages forin vitro responses to particulate antigens.Journal of Experimental Medicine,149, 793–807.
Cameron, D. J., andChurchill, W. H., 1980, Cytotoxicity of human macrophages for tumor cells: enhancement by bacterial lipopolysaccharides (LPS).Journal of Immunology,124, 708–712.
Vogel, S. N., Hilfiker, M. L., andCaulfield, M. J., 1983, Endotoxin-induced T lymphocyte proliferation.Journal of Immunology,130, 1774–1779.
Salata, R. A., Kleinhenz, M. E., Schacter, B. Z., andEllner, J. J., 1984, Augmentation of natural killer cell activity by lipopolysaccharide through separable effects on the binding of nonadherent lymphocytes to tumor targets and tumor killing.Cancer Research,44, 1044–1047.
Morrison, D. C., andUlevitch, R. J., 1978, The effects of bacterial endotoxins on host mediation systems.American Journal of Pathology,93, 527–617.
Carswell, E. A., Old, R. L., Kassel, S., Green, N., Fiore, B., andWilliamson, B., 1975, An endotoxin-induced serum factor that causes necrosis of tumors.Proceedings of the National Academy of Sciences of the U.S.A.,72, 3666–3670.
Blanchard, D. K., Djeu, J. Y., Klein, T. W., Friedman, H., andStewart, W. E., 1986, Interferon-γ induction by lipopolysaccharide: dependence on interleukin 2 and macrophages.Journal of Immunology,136, 963–970.
Hanna, N., andFidler, I. J., 1980, Role of natural killer cells in the destruction of circulating tumor emboli.Journal of the National Cancer Institute,65, 801–809.
Fidler, I. J., Sone, S., Fogler, W. E., andBarnes, Z. L., 1981, Eradication of spontaneous metastases and activation of alveolar macrophage by intravenous injection of liposomes containing muramyl dipeptide.Proceedings of the National Academy of Sciences of the U.S.A.,78, 1680–1684.
Hanna, N., 1985, The role of natural killer cells in the control of tumor growth and metastasis.Biochimica et Biophysica Acta,780, 213–226.
Wright, S. D., Ramos, R. A., Tobias, P. S., Ulevitch, R. J., andMathison, J. C., 1990, CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein.Science,249, 1431–1433.
Diana, M. J.,Dianna, B. R.,John, H. E., andAllen, J. R., 1983, Binding of bacterial lipopolysaccharide to murine lymphocytes.Annals of the New York Academy of Sciences, 72–80.
Goguel, A. F., andNauciel, C., 1977, Inhibition of tumor growth by the peptidoglycan from bacillus megaterium.Journal of the National Cancer Institute,59, 1723–1726.
Tokunaga, T., Yamamoto, H., Shimada, S., Abe, H., Fukuda, T., Fujisawa, Y., Furutani, Y., Yano, O., Kataoka, T., Sudo, T., Makiguchi, N., andSuganuma, T., 1984, Antitumor activity of deoxyribonucleic acid fraction from mycobacterium bovis BCG. 1. isolation, physicochemical characterization, and antitumor activity.Journal of the National Cancer Institute,72, 955–962.
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Jibu, T., Ando, K., Matsumoto, T. et al. Active components of intestinal bacteria for abdominal irradiation-induced inhibition of lung metastases. Clin Exp Metast 9, 529–540 (1991). https://doi.org/10.1007/BF01768581
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DOI: https://doi.org/10.1007/BF01768581