Abstract
The effect of Lactobacillus casei YIT9018 (LC 9018) on a highly metastatic variant of B16 melanoma, B16-BL6, was determined in C57BL/6 mice. Intralesional (i.l.) injection of LC 9018 inhibited tumor growth and prolonged the survival after s.c. inoculation of B16-BL6 into C57BL/6 mice. Injection of LC 9018 i.v. protected the mice against pulmonary metastasis after i.v. inoculation of B16-BL6. Injection of LC 9018 i.l. before surgical excision of the primary tumor inhibited axillary lymph node metastasis and i.v. injection of LC 9018 after surgical excision of the primary tumor inhibited both axillary lymph node and lung metastases. On the other hand, the combination of i.l. and i.v. injections of LC 9018 markedly inhibited both lymph node and lung metastases. Natural killer cell activity of axillary lymph node cells was augmented by the injection of LC 9018 into a front footpad, while the cytolytic activity of axillary lymph node cells was significantly enhanced. However, the cytolytic activity was diminished by depleting whole lymph node cells of the plastic adherent cells. Furthermore, alveolar macrophage-mediated cytotoxic activity was augmented by the i.v. injection of LC 9018.
Keywords: Melanoma, Primary Tumor, Lymph Node Metastasis, Natural Killer, Natural Killer Cell
References
- 1.Azuma I, Yamawaki M, Ogura T, Yoshimoto T, Tokuzen R, Hirao F, Yamamura Y. Antitumor activity of BCG cell-wall skeleton and related materials. Gann. 1978;21:73. [Google Scholar]
- 2.Azuma I, Yamawaki M, Yoshimoto T, Saiki I, Uemiya M, Tanio Y, Tokuzen R, Yasumoto K, Yamamura Y. Antitumor activity of cell-wall skeleton of Propionibacterium acnes C7 in mice and guinea pigs. Gann. 1979;70:737. [PubMed] [Google Scholar]
- 3.Fidler IJ, Kripke ML. Metastasis results from preexisting variant cells within a malignant tumor. Science. 1977;197:893. doi: 10.1126/science.887927. [DOI] [PubMed] [Google Scholar]
- 4.Fidler IJ, Nicolson GL. Fate of recirculating B16 melanoma metastatic variant cells in parabiotic syngeneic recipients. J Natl Cancer Inst. 1977;58:1867. doi: 10.1093/jnci/58.6.1867. [DOI] [PubMed] [Google Scholar]
- 5.Fidler IJ, Fogler WE, Tarcsay L, Schumann G, Braun DG, Schroit AJ. Systemic activation of macrophages and treatment of cancer metastases by liposomes containing hydrophilic or lipophilic muramyl dipetide. In: Hadden JW, editor. Advances in pharmacology 2. Oxford: Pergamon Press; 1983. p. 235. [Google Scholar]
- 6.Gorelik E, Wiltrout RH, Okumura K, Have S, Herberman RB. Role of NK cells in the control of metastatic spread and growth of tumor cells in mice. Int J Cancer. 1982;30:107. doi: 10.1002/ijc.2910300118. [DOI] [PubMed] [Google Scholar]
- 7.Gorelik E, Bere WW, Herberman RB. Role of NK cells in the antimetastatic effect of anticoagulant drugs. Int J Cancer. 1984;33:87. doi: 10.1002/ijc.2910330115. [DOI] [PubMed] [Google Scholar]
- 8.Hanna MG, Jr, Peters LC. Immunotherapy of established micrometastases with bacillus Calmette-Guérin tumor cell vaccine. Cancer Res. 1978;38:204. [PubMed] [Google Scholar]
- 9.Hanna N, Burton RC. Definitive evidence that natural killer (NK) cells inhibit experimental tumor metastasis in vivo. J Immunol. 1981;127:1754. [PubMed] [Google Scholar]
- 10.Hart IR. The selection and characterization of an invasive variant of the B16 melanoma. Am J Pathol. 1979;97:587. [PMC free article] [PubMed] [Google Scholar]
- 11.Herberman RB (1983) Natural killer cells and other effector cells, and their roles in resistance against cancer. In: Herberman RB, Friedman F (eds) The reticuloendothelial systems, vol. 5, Plenum Publishing Corp., p 279
- 12.Kato I, Kobayashi S, Yokokura T, Mutai M. Antitumor activity of Lactobacillus casei in mice. Gann. 1981;72:517. [PubMed] [Google Scholar]
- 13.Kato I, Yokokura T, Mutai M. Augmentation of mouse natural killer cell activity of Lactobacillus casei and its surface antigens. Microbiol Immunol. 1984;28:209. doi: 10.1111/j.1348-0421.1984.tb00672.x. [DOI] [PubMed] [Google Scholar]
- 14.Key ME. Macrophages in cancer metastases and their relevance to metastatic growth. Cancer Metastasis Rev. 1983;2:75. doi: 10.1007/BF00046906. [DOI] [PubMed] [Google Scholar]
- 15.Matsuzaki T, Yokokura T, Azuma I. Antitumor activity of Lactobacillus casei on Lewis lung carcinoma and Line-10 hepatoma in syngeneic mice and guinea pigs. Cancer Immunol Immunother. 1985;20:18. doi: 10.1007/BF00199768. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Miake S, Nomoto K, Yokokura T, Yoshikai Y, Mutai M, Nomoto K. Protective effect of Lactobacillus casei on Pseudomonas aeruginosa infection in mice. Infect Immun. 1985;48:480. doi: 10.1128/iai.48.2.480-485.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Ogura T, Namba M, Yamamura Y, Azuma I. Immunotherapeutic effect of BCG and Nocardia rubra cell-wall skeleton on syngeneic tumors in rats. In: Terry WD, Yamamura Y, editors. Immunobiology and immunotherapy of cancer. New York: Elsevier North/Holland, Inc.; 1979. p. 295. [Google Scholar]
- 18.Poste G, Doll J, Hart IR, Fidler IJ. In vitro selection of murine B16 melanoma variants with enhanced tissue-invasive properties. Cancer Res. 1980;40:1636. [PubMed] [Google Scholar]
- 19.Ramani P, Hart IR, Balkwill FR. The effect of interferon on experimental metastases in immunocompetent and immunodeficient mice. Int J Cancer. 1986;37:563. doi: 10.1002/ijc.2910370415. [DOI] [PubMed] [Google Scholar]
- 20.Saijo N, Ozaki A, Beppu Y, Shibuya M, Shimizu E, Hoshi A (1984) Detailed analysis of artificial and spontaneous tumor metastases in mice with depressed natural killer activity by anti-asialo GM1 antibody. In: Hoshino T, Koren HB, Uchida A (eds) Natural killer activity and its regulation. Excerpta Medica, p 358
- 21.Sone S, Fidler IJ. In situ activation of tumoricidal properties in rat alveolar macrophages and rejection of experimental lung metastases by intravenous injection of Nocardia rubra cell wall skeleton. Cancer Immunol Immunother. 1982;12:203. [Google Scholar]
- 22.Sone S, Pollack VA, Fidler IJ. Direct activation of tumoricidal properties in rat alveolar macrophages by Nocardia rubra cell wall skeleton. Cancer Immunol Immunother. 1980;9:227. [Google Scholar]
- 23.Tanio Y, Sohma H, Tokushima Y, Nishimura K, Saiki I, Azuma I. Comparison of antimetastatic effect against Lewis lung carcinoma after intratumoral and intravenous injections of cell-wall skeleton of Propionibacterium acnes C7 in C57BL/6 mice. Gann. 1984;75:237. [PubMed] [Google Scholar]
- 24.Tsuruo T, Naganuma K, Yamori T, Kawabata H, Oh-hara T, Iida H, Tsukagoshi S, Sakurai Y. Spontaneous metastasis of highly metastatic variants of mouse tumors and the effect of drugs on the metastasis. Gann. 1984;75:557. [PubMed] [Google Scholar]
- 25.Tsuruo T, Yamori T, Naganuma K, Hori K, Kawabata H, Tsukagoshi S, Sakurai Y. Metastasis after intravenous inoculation of highly metastatic variants of mouse tumors and the effect of several antitumor drugs on the tumors. Gann. 1984;75:193. [PubMed] [Google Scholar]
- 26.Vosika GJ. Clinical immunotherapy trials of bacterial components derived from Mycobacteria and Nocardia . J Biol Response Mod. 1983;2:321. [PubMed] [Google Scholar]
- 27.Yamamura Y, Ogura T, Sakatani M, Hirao F, Kishimoto S, Fukuoka M, Takada M, Kawahara M, Furuse K, Kawahara O, Ikegami H, Ogawa N. Randomized controlled study of adjuvant immunotherapy with Nocardia rubra cell wall skeleton for inoperable lung cancer. Cancer Res. 1983;43:5575. [PubMed] [Google Scholar]
- 28.Zbar B, Rapp HJ, Ribi E. Tumor suppression by cell walls of Mycobacterium bovis attached to oil droplets. J Natl Cancer Inst. 1972;48:831. [PubMed] [Google Scholar]
