The effect of GM-CSF and G-CSF on the growth of human osteosarcoma cells in vitro and in vivo.
The human osteosarcoma cell line, MG63, responds both to GM-CSF and to G-CSF in vitro. To assess the significance of these observations to tumor growth in vivo, MG63 cells were engineered by retroviral infection to produce human GM-CSF or G-CSF. These retrovirally infected cells become autostimulatory as measured by increased [3H]-thymidine incorporation (3- to 7-fold) and anchorage-independent colony formation (7- to 10-fold) as compared with uninfected MG63 cells or cells infected with control (neor) retrovirus. The increased proliferation induced by exogenous GM-CSF or G-CSF on uninfected MG63 cells in both assays could be completely inhibited by anti-GM-CSF or anti-G-CSF antibodies, while the same antibodies only partially abrogated proliferation by the growth-factor-producing cells. None of 34 nude or SCID mice developed tumors when injected s.c. with uninfected or neor-virus-infected cells. In contrast, all 30 mice injected with GM-CSF- or G-CSF-producing MG63 cells developed tumors which were G418-resistant and factor-producing. Tumor cell DNA showed a polyclonal retroviral integration pattern indistinguishable from that in the DNA of cells injected into mice. Tumors that formed following injection of a mixture of G418-resistant, GM-CSF-producing cells and cells infected with virus containing only the hygror gene contained hygromycin-resistant cells in the same proportion as was present in the original cell mixture. These data indicate that GM-CSF and G-CSF can support the growth of an osteosarcoma cell line both in vitro and in vivo whether the factor is supplied by autocrine production or from exogenous sources.
Thacker
J D
JD
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, Canada.
Dedhar
S
S
Hogge
D E
DE
D016475:3T3 Cells / Q000382:microbiology; D000818:Animals; D015139:Blotting, Southern; D001859:Bone Neoplasms / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D015197:Carcinogenicity Tests; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008747:Methylcellulose / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D012516:Osteosarcoma / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008747:Methylcellulose