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Hypoxia down‐regulates MCP‐1 expression: implications for macrophage distribution in tumors
Author(s) -
Negus Rupert P. M.,
Turner Lynn,
Burke Frances,
Balkwill Frances R.
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.63.6.758
Subject(s) - biology , hypoxia (environmental) , macrophage , microbiology and biotechnology , distribution (mathematics) , cancer research , genetics , oxygen , chemistry , organic chemistry , in vitro , mathematical analysis , mathematics
Monocyte chemoattractant protein 1 (MCP‐1) is likely to contribute to the macrophage infiltrate in human ovarian carcinomas. Although MCP‐1 is predominantly expressed by the tumor parenchyma, macrophages accumulate at highest density in necrotic regions, which are associated with low oxygen tensions. Tumor necrosis factor α (TNF‐α) can stimulate MCP‐1 production and is also present within ovarian carcinomas. We have investigated the effect of hypoxia both on MCP‐1 expression in ovarian cancer cell lines and monocyte migration. Hypoxia down‐regulated TNF‐α‐induced MCP‐1 mRNA and protein production by ovarian cancer cells. The effect was mimicked by cobalt chloride and desferrioxamine, consistent with a specific oxygen‐sensing mechanism. Unlike antioxidants, hypoxia did not inhibit nuclear factor κB mobilization. Monocyte migration in response to MCP‐1 was also diminished under hypoxic conditions. Down‐regulation of MCP‐1 expression and the inhibition of monocyte migration are independent effects of hypoxia that may contribute to the distribution of macrophages within ovarian tumors. J. Leukoc. Biol . 63: 758–765; 1998.