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IL‐12 regulates VEGF and MMPs in a murine breast cancer model
Author(s) -
Dias Sergio,
Boyd Robert,
Balkwill Frances
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19981029)78:3<361::aid-ijc17>3.0.co;2-9
Subject(s) - vegf receptors , matrix metalloproteinase , breast cancer , cancer research , medicine , cancer , biology , oncology
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‐γ reduced tumor cell production of VEGF over a 24‐hr period in vitro , suggesting that IL‐12‐induced IFN‐γ 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. Int. J. Cancer 78:361–365, 1998.© 1998 Wiley‐Liss, Inc.