title: Production of colony-stimulating factor by tumor cells and the factor-mediated induction of suppressor cells.
abstract: Spleen mononuclear cells of C3H/HeN mice were cultivated with mitomycin C-treated tumor cells, X5563, MH134, MM48, MM46, and FM3A/R, all of which were of syngeneic origin, in a medium containing normal syngeneic mouse serum but not FCS. There was a proliferative response to X5563, MH134, and MM48, but not to the two other tumor cells, MM46 and FM3A/R. The responder spleen cells were found to be nonadherent cells with a phenotype of Thy-1-L3T4-Lyt2-Ig-Macl-, which were neither mature T and B cells nor mature macrophage/granulocytes. It was also found that the proliferation of these nonadherent no-marker cells was mediated by tumor cell-derived soluble factors but not by direct stimulation with tumor cells. The responsible factor was a molecule(s) with a Mr of 23 to 25 kDa, which had a CSF activity inducing granulocyte (G)-, macrophage (M)- and G + M-colonies in the bone marrow cells. Neutralization tests of this factor-induced proliferation of spleen cells revealed that a major part of the factor may be GM-CSF or a molecule closely related to it. Incubation of spleen mononuclear cells with these GM-CSF-like tumor cell factors resulted in induction of myeloblastic/promyelocytic cells with a phenotype of Mac-1+2+Ia+ Thy-1-L3T4-Lyt2-Ig- in the spleen cell cultures, which could suppress mitogenic responses of the spleen cells to T and B cell mitogens. GM-CSF-like activity could also be detected in the serum of mice bearing X5563, MH134, and MM48, but not in those bearing MM46 and FM3A/R. Subcutaneous inoculation of C3H/HeN mice with these X5563, MH134, and MM48 tumor cells generated massive metastasis in the lung and lymph nodes, whereas MM46 and FM3A/R produced no macroscopic tumor cell metastasis. These results strongly suggest the possibility that in some tumor cell-host systems, a GM-CSF-like factor(s) produced constitutively by the tumor cells may play an important role in the development of tumor metastasis, mediating through suppression of lymphoid tissues of the host.
authors.affiliation: Department of Microbiology, Tohoku University School of Dentistry, Sendai, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tsuchiya
authors.forename: M
authors.initials: M
authors.lastname: Igarashi
authors.forename: R
authors.initials: R
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Kumagai
mesh_terms: D000818:Animals; D000954:Antigens, Surface; D002474:Cell-Free System; D003115:Colony-Stimulating Factors / Q000096:biosynthesis* / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000949:Histocompatibility Antigens Class II; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D016177:Macrophage-1 Antigen; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000502:physiology; D009374:Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D013154:Spleen / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000276:immunology*
chemical_list: D000954:Antigens, Surface; D003115:Colony-Stimulating Factors; D000949:Histocompatibility Antigens Class II; D016177:Macrophage-1 Antigen; D009363:Neoplasm Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor