Hypoxia down-regulates MCP-1 expression: implications for macrophage distribution in tumors.

Abstract:

: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 alpha (TNF-alpha) 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-alpha-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 KB 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.

journal_name

J Leukoc Biol

authors

Negus RP,Turner L,Burke F,Balkwill FR

doi

10.1002/jlb.63.6.758

subject

Has Abstract

pub_date

1998-06-01 00:00:00

pages

758-65

issue

6

eissn

0741-5400

issn

1938-3673

journal_volume

63

pub_type

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