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

✍ Scribed by Sergio Dias; Robert Boyd; Frances Balkwill

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: French
• Weight: 255 KB
• Volume: 78
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19981029)78:3<361::aid-ijc17>3.0.co;2-9

✦ Synopsis

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-␥ reduced tumor cell production of VEGF over a 24-hr period in vitro, suggesting that IL-12-induced IFN-␥ 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.