Inhibitory effect of locally produced and exogenous interleukin-6 on tumor growth in vivo.
In order to define the potential antitumor activity of the multifunctional cytokine interleukin-6 (IL-6), retrovirus-mediated gene transfer was used to introduce and express a cDNA encoding human IL-6 in the murine fibrosarcoma cell line Fsa-R. Although these genetically modified tumor cells appeared morphologically and phenotypically identical to control Fsa-R cells and had a similar plating efficiency in vitro, they were found to exhibit greatly reduced tumorigenicity in vivo following intravenous injection into syngeneic recipients. Exogenous IL-6 was shown to produce a similar inhibition of tumor growth in the lung if administered intraperitoneally. In contrast, tumor growth in subcutaneous sites was inhibited only if the tumor cells were engineered to express IL-6 locally, or if IL-6 was administered intratumorally. Intraperitoneal injection of IL-6 had no inhibitory effect. Tumors that did grow from IL-6-producing tumor cell inocula in subcutaneous sites were found to contain large numbers of macrophages. These results demonstrate that the antitumor activity of systemically administered IL-6 varies depending on the site of tumor growth and suggest an important role for IL-6 in the recruitment, proliferation and/or survival of tumor-associated macrophages.
Dougherty
G J
GJ
Terry Fox Laboratory, B.C. Cancer Research Centre, Vancouver, Canada.
Thacker
J D
JD
Lavey
R S
RS
Belldegrun
A
A
McBride
W H
WH
D000818:Animals; D002469:Cell Separation; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology / Q000628:therapy*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D012074:Remission Induction; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D011994:Recombinant Proteins