ANTITUMOR EFFECTS OF HUMAN RECOMBINANT MACROPHAGE-COLONY-STIMULATING FACTOR AGAINST RAT-BRAIN TUMORS

The tumoricidal effects of M-CSF were examined using two subcutaneousl y-transplanted rat brain tumor cell lines, 9L and T9 gliomas. In rats treated with high-dose M-CSF (16 million U/kg administered for 4 days a week for 3 weeks), 9L glioma growth was inhibited by 81.9% following subcutaneous (s.c.) injection and by 70.5% after intraperitoneal (i.p .) injection and T9 glioma growth was inhibited by 69.2% after i.p. in jection. After short-term treatment with high-dose M-CSF (32 million U /kg administered s.c. for 6 consecutive days, 9L glioma growth was inh ibited by 82.1%. All these inhibitory effects differed significantly c ompared with the respective untreated control groups. However, treatme nt with low-dose M-CSF (1.6 million U/kg administered s.c. for 4 days a week for 3 weeks) showed no significant effects against 9L and T9 gl ioma growth compared with the untreated controls. No significant effec ts of M-CSF against cell proliferation, measured as PCNA expression, w ere observed in any group. Significant hematopoietic effects on the le ukocyte counts were observed only in the groups treated with high dose M-CSE These results suggest that M-CSF at a high dose which produces hematopoietic effects on peripheral leukocytes inhibits the growth of gliomas. This inhibitory effect may have been due to a tumoricidal mec hanism of M-CSF that depended on the production or release of some hem atopoietic soluble factors, but was independent of PCNA expression by the tumors.