GM-CSF-transduced B16 melanoma cells are highly susceptible to lysis by normal murine macrophages and poorly tumorigenic in immune-compromised mice.
Granulocyte-macrophage colony-stimulating factor (GM-CSF)-transduced B16-F10 murine melanoma cells had lower tumorigenicity in both syngeneic and nude mice than parental or LacZ-transduced (control) cells. The subcutaneous (s.c.) tumors producing GM-CSF were densely infiltrated with macrophages, whereas the control tumors were not. In vitro studies showed that GM-CSF-transduced B16 cells were susceptible to lysis mediated by nonactivated murine macrophages, whereas control B16 cells were not. Macrophage-mediated cytotoxicity against GM-CSF-transduced B16 cells was independent of the presence of NO, H2O2, O2-, tumor necrosis factor alpha, and matrix metalloproteinase. Coculture experiments using GM-CSF-producing and -nonproducing B16 cells demonstrated that GM-CSF produced by the transduced B16 cells activated macrophages to kill the bystander non-GM-CSF-producing tumor cells. The results suggest that GM-CSF released by tumor cells can induce macrophage-mediated cytotoxicity, which in turn can inhibit the in vivo growth of GM-CSF-transduced tumor cells.
Kumar
R
R
Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Yoneda
J
J
Fidler
I J
IJ
Dong
Z
Z
D000818:Animals; D003602:Cytotoxicity, Immunologic; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D016867:Immunocompromised Host; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D016178:Granulocyte-Macrophage Colony-Stimulating Factor