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Contribution of the CXC chemokines IP‐10 and Mig to the antitumor effects of IL‐12
Author(s) -
Kanegane Chiharu,
Sgadari Cecilia,
Kanegane Hirokazu,
TeruyaFeldstein Julie,
Yao Lei,
Gupta Ghanshyam,
Farber Joshua M.,
Liao Fang,
Liu Li,
Tosato Giovanna
Publication year - 1998
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.64.3.384
Subject(s) - biology , cxc chemokine receptors , chemokine , immunology , cancer research , immune system , chemokine receptor
The mechanisms by which interleukin‐12 (IL‐12) exerts antitumor effects have been difficult to dissect. In this study, we examined the potential contribution of the chemokines interferonγ‐inducible protein‐10 (IP‐10) and Mig to the antitumor effects of IL‐12. Using an athymic mouse model, local inoculations with IL‐12 consistently produced tumor size reductions associated with characteristic tumor necrosis and vascular damage. These effects were indistinguishable from those produced by IP‐10 or Mig injected locally in the same tumor model. Local and systemic treatment with IL‐12 was associated with expression of the interferon‐γ (IFN‐γ), IP‐10, and Mig genes and proteins in the tumor. Levels of IP‐10 and Mig expression in the tumor, the liver, and the kidney were inversely correlated with tumor size. Administration in vivo of neutralizing antibodies to IP‐10 and Mig reduced substantially the antitumor effects of IL‐12 inoculated locally into the tumors. These results support the notion that IP‐10 and Mig contribute to the antitumor effects of IL‐12 through their inhibitory effects on tumor vasculature. J. Leukoc. Biol . 64: 384–392; 1998.