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Induction and Testing of Hypoxia in Cell Culture
07:01

Induction and Testing of Hypoxia in Cell Culture

Published on: August 12, 2011

Macrophage migration inhibitory factor activates hypoxia-inducible factor in a p53-dependent manner

Seiko Oda1, Tomoyuki Oda, Kenichiro Nishi

  • 1Department of Anesthesia, Kyoto University Hospital, Kyoto University, Kyoto, Japan.

Plos One
|May 22, 2008
PubMed
Abstract

Insights

Macrophage migration inhibitory factor (MIF) regulates hypoxia-inducible factor 1 (HIF-1) activity via a p53-dependent mechanism. This finding reveals a molecular pathway through which MIF promotes tumor progression and invasiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Macrophage migration inhibitory factor (MIF) is a cytokine involved in inflammation, tumor progression, and neovascularization.
  • MIF is induced by hypoxia in a hypoxia-inducible factor 1 (HIF-1)-dependent manner.
  • Overexpression of MIF is observed in various human tumors.

Purpose of the Study:

  • To investigate the effect of MIF on HIF-1 activity in human cancer cells.
  • To elucidate the molecular mechanisms underlying MIF-mediated HIF-1 activation.

Main Methods:

  • Experiments were conducted using human breast cancer cell lines (MCF-7, MDA-MB-231) and osteosarcoma cells (Saos-2).
  • Intracellular MIF overexpression and extracellular MIF administration were employed.
  • Mutagenesis analysis of MIF and p53 knockdown were performed.
  • The role of the MIF receptor CD74 was assessed.

Main Results:

  • Intracellular MIF overexpression and extracellular MIF administration enhanced HIF-1 activation under hypoxia in MCF-7 cells.
  • MIF-mediated HIF-1 activation was dependent on wild-type p53, not MIF's redox activity.
  • The MIF receptor CD74 was implicated in extracellular MIF-induced HIF-1 activation.

Conclusions:

  • MIF regulates HIF-1 activity through a p53-dependent pathway.
  • This functional link between MIF and HIF-1 provides a molecular mechanism for MIF's role in promoting tumorigenesis.
  • MIF's involvement in cell proliferation, survival, angiogenesis, and tumor invasiveness is further supported.

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