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Interleukin‐18 acts as an angiogenesis and tumor suppressor
Author(s) -
CAO RENHAI,
FARNEBO JACOB,
KURIMOTO MASASHI,
CAO YIHAI
Publication year - 1999
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.13.15.2195
Subject(s) - angiogenesis , cytokine , fibrosarcoma , neovascularization , chorioallantoic membrane , cancer research , basic fibroblast growth factor , fibroblast growth factor , in vivo , interleukin , endothelial stem cell , biology , immunology , growth factor , in vitro , medicine , pathology , receptor , microbiology and biotechnology , biochemistry
Interleukin‐18 (IL‐18), also called interferon‐γ (IFN‐γ)‐inducing factor, has recently been characterized as a potent IFN‐γ‐inducing cytokine. We now report that IL‐18 is a novel antiangiogenic and antitumor cytokine. In vitro , IL‐18 specifically inhibits fibroblast growth factor‐2‐stimulated proliferation of capillary endothelial cells. In vivo , IL‐18 is sufficiently potent to suppress the fibroblast growth factor‐induced corneal neovascularization by systemic administration in mice. This cytokine also inhibits embryonic angiogenesis in the chick chorioallantoic membrane assay. Systemic and intralesional administrations of IL‐18 produce a significant suppression of the growth of murine T241 fibrosarcoma in syngeneic C57Bl6/J and immunodeficient SCID mice. The antitumor effect appears to be potent because an average of >75% inhibition of primary tumor growth was observed at a dose of 50 µg/kg/day. In cell culture, murine T241 fibrosarcoma cells are insensitive to recombinant IL‐18 at concentrations that significantly inhibit endothelial cell proliferation. Immunohistochemical studies of tumor tissues reveal hypovascularization of the IL‐18‐treated tumors. These results suggest that IL‐18 may participate in the regulation of a switch of tumor angiogenesis.—Cao, R., Farnebo, J., Kurimoto, M., Cao, Y. Interleukin‐18 acts as an angiogenesis and tumor suppressor. FASEB J. 13, 2195–2202 (1999)