PROTEIN-BOUND POLYSACCHARIDE PSK ABROGATES MORE EFFICIENTLY EXPERIMENTAL METASTASES DERIVED FROM H-2 NEGATIVE THAN FROM H-2 POSITIVE FIBROSARCOMA TUMOR CLONES

We studied the effect of protein-bound polysaccharide PSK on metastati c colonization of BALB/c mice after intravenous injections of differen t syngeneic murine H-2 positive and H-2 negative tumor clones. The tum or lines used were different clones from chemically induced fibrosarco mas (GR9.B9, an H-2 negative clone from GR9 tumor, and B7.1.B4, an H-2 positive clone from B7.1 tumor). These clones were selected because o f their different sensitivity to NK cytotoxicity, which was related to MHC class I expression. Pretreatment of mice with PSK inhibited metas tatic colonization derived from B9 H-2 negative tumor cells. In contra st, lung colonization of PSK treated mice injected with B7.1.B4 H-2 po sitive tumor cells was higher, and differences in the number of coloni es between untreated and PSK treated mice were small. In several exper iments the effect of PSK was attenuated to a greater degree when high numbers of cells were injected. Abrogation of NK cells with anti-asial o GM1 serum significantly increased (in all tumors and at different ce ll doses) the number of metastatic colonies in comparison with untreat ed mice injected with tumors, regardless of the cell dose used. These results clearly suggest that NK cell activation in vivo by the protein bound polysaccharide PSK abrogates metastasis formation in mice. Abro gation was dependent on the H-2 phenotype even when pretreatment consi sted of a single dose of PSK. This effect, related to the NK sensitivi ty of the tumor target, can be used to predict the effect of PSK in vi vo.