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Int J Cancer. 1998 Oct 29;78(3):361-5.

IL-12 regulates VEGF and MMPs in a murine breast cancer model.

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Biological Therapies Laboratory, Imperial Cancer Research Fund, London, UK.


In a murine model of breast cancer, IL-12 therapy exerts potent anti-angiogenic effects which contribute to tumor regression. After 7 days of treatment, levels of tumor VEGF protein decline markedly and are undetectable at 14 days. This decline is accompanied by a fall in MMP-9 and, as the tumors regress, an increase in its natural inhibitor, TIMP-1. A cell line established from the primary tumor produced VEGF in vitro. IFN-gamma reduced tumor cell production of VEGF over a 24-hr period in vitro, suggesting that IL-12-induced IFN-gamma may be responsible for the decline in VEGF levels in vivo. There is also in vitro evidence that IL-12 regulates stromal cell interactions, leading to decreased MMP-9 and increased TIMP-1 production. Thus, we suggest that at least 2 mechanisms are involved in IL-12 regulation of angiogenesis, removing the pro-angiogenic stimulus and blocking the release and activity of MMPs.

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