Recombinant human granulocyte colony-stimulating factor inhibits the metastasis of hematogenous and non-hematogenous tumors in mice.
We studied the effects of in vivo administrations of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the metastasis of murine hematogenous and non-hematogenous tumors in spontaneous and experimental metastasis models. Spontaneous lung metastasis caused by intra-footpad injections of B16-BL6 melanoma and Lewis-lung-carcinoma (3LL) cells were inhibited by intravenous (i.v.) and subcutaneous (s.c.) injections of rhG-CSF after excision of the primary tumors. Recombinant hG-CSF significantly inhibited liver metastasis when administered i.v. after i.v. injection of L5178Y-ML25 T-lymphoma cells. Multiple i.v. administration of rhG-CSF after the tumor inoculation prolonged the survival times of mice inoculated i.v. with L5178Y-ML25 lymphoma cells. Recombinant hG-CSF did not directly affect the growth of B16-BL6 and L5178Y-ML25 cells in vitro. During the administration periods, both i.v. and s.c. injections of rhG-CSF increased the number of total white blood cells (WBC) in peripheral blood to approximately 3 times the normal level in normal and tumor-bearing mice. We also found that the administration of rhG-CSF stimulates neutrophils to become cytostatic against these tumor cells. Our results indicate that the injection of rhG-CSF is effective in inhibiting lung and liver metastases by activating neutrophils and increasing cell number.
Matsumoto
Y
Y
Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Saiki
I
I
Murata
J
J
Okuyama
H
H
Tamura
M
M
Azuma
I
I
D000818:Animals; D002277:Carcinoma / Q000097:blood / Q000556:secondary*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007958:Leukocyte Count; D008113:Liver Neoplasms / Q000097:blood / Q000556:secondary*; D008175:Lung Neoplasms / Q000097:blood / Q000556:secondary*; D008546:Melanoma, Experimental / Q000097:blood / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011994:Recombinant Proteins / Q000494:pharmacology
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor