Fibrosarcoma cells transduced with the IL-6 gene exhibited reduced tumorigenicity, increased immunogenicity, and decreased metastatic potential.
Murine fibrosarcoma cell lines transduced with retroviral vectors containing the murine interleukin 6 (IL-6) gene constitutively secreted IL-6. When injected s.c. into normal mice these IL-6-secreting tumors exhibited reduced tumorigenicity. This reduced tumorigenicity was not seen in nude or irradiated mice, implicating a T-cell-dependent, radiosensitive host response activated by the cytokine. Subcutaneous IL-6-secreting tumor did not retard the growth of distant deposits of wild-type tumor in the same host. However, animals rejecting IL-6-secreting tumors exhibited resistance to later challenge with wild-type tumor. When injected i.v. in an experimental metastasis model the IL-6-secreting tumors failed to or were extremely inefficient in giving rise to pulmonary nodules; this was observed in both normal and immunoincompetent mice, implicating a second, nonimmune mechanism affecting the growth of the tumor modified to secrete IL-6.
Mullen
C A
CA
Metabolism Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Coale
M M
MM
Levy
A T
AT
Stetler-Stevenson
W G
WG
Liotta
L A
LA
Brandt
S
S
Blaese
R M
RM
D000818:Animals; D005260:Female; D005354:Fibrosarcoma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006084:Graft Rejection; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D016867:Immunocompromised Host; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008748:Methylcholanthrene; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D015395:Histocompatibility Antigens Class I; D015850:Interleukin-6; D008748:Methylcholanthrene