[Antitumor effect of PSK (2): effector mechanism of the antimetastatic effect in the "double grafted tumor system"].
The antimetastatic effect of PSK was analysed with the "double grafted tumor system" in which BALB/c mice received simultaneous intradermal inoculations of Meth-A in the right (10(6) cells) and left (2 X 10(5) cells) flanks and were then injected with PSK in the right tumor on day 3. PSK inhibited the growth of not only the right but also the left, non-treated tumor. Immunized spleen cells were taken from mice which had been cured by the intratumoral administration of 5 mg of PSK. On day 3, one hour after intravenous injection of cyclophosphamide, immunized spleen cells (2 X 10(7) cells/mouse) were injected into the Meth-A tumor. Adoptive transfer of PSK immunized spleen cells caused the complete regression of Meth-A tumors. The effector cell activity was lost only after treatment with anti-Lyt-1 monoclonal antibody plus complement. Spleen cells and right and left regional (axillary and inguinal) lymph node cells prepared from PSK immunized mice 7 and 14 days after tumor inoculation were examined for Thy-1, Lyt-1, Lyt-2 and asialo GM1 phenotypes by flow cytometric analysis. The number of Lyt-1 positive lymphocytes increased in the right regional lymph nodes after intratumoral administration of PSK. Immunohistochemical analyses of the right and left tumors in the "double grafted tumor system" on day 7 and day 14 were carried out by PAP (peroxidase antiperoxidase) method. Necrosis, karyoklasis and a massive accumulation of macrophages were found in the right tumor after intratumoral administration of PSK. An infiltration of macrophages and Lyt-2 positive lymphocytes was found in the left, non-treated tumor. These results suggest that intratumoral administration of PSK might induce Lyt-1 positive cells first in regional lymph nodes, then in the spleen, and subsequently induce macrophages and Lyt-2 positive cells in the left, non-treated tumor of the "double grafted tumor system", thus bringing about the regression of metastatic tumors.
D000818:Animals; D005354:Fibrosarcoma / Q000276:immunology / Q000473:pathology; D007116:Immunization, Passive; D007694:Killer Cells, Natural / Q000276:immunology; D008114:Liver Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D008262:Macrophage Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009368:Neoplasm Transplantation; D011509:Proteoglycans / Q000627:therapeutic use*
D011509:Proteoglycans; C010770:polysaccharide-K