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Macrophage migration inhibitory factor promotes intestinal tumorigenesis
Jonathan M Wilson1, P Louise Coletta, Richard J Cuthbert
1Molecular Medicine Unit, University of Leeds, Leeds, United Kingdom.
Gastroenterology
|November 16, 2005
Summary
Macrophage migration inhibitory factor (MIF) promotes early intestinal tumor growth and angiogenesis. Inhibiting MIF may be a viable strategy for colorectal cancer chemoprevention.
Area of Science:
- Gastroenterology
- Oncology
- Molecular Biology
Background:
- Macrophage migration inhibitory factor (MIF) is present in the human gastrointestinal tract.
- MIF exhibits protumorigenic activity in various cancer models.
- Its role in early intestinal tumorigenesis requires investigation.
Purpose of the Study:
- To investigate the expression and function of MIF in early intestinal tumorigenesis.
- To determine if MIF is a potential target for colorectal cancer chemoprevention.
Main Methods:
- Measured MIF mRNA, protein, and activity in human colorectal adenomas and ApcMin/+ mice.
- Assessed MIF function using human colorectal adenoma cells in vitro.
- Evaluated the impact of genetic MIF deletion on ApcMin/+ mouse intestinal tumorigenesis.
Main Results:
- MIF expression and activity were elevated in intestinal adenomas from humans and ApcMin/+ mice.
- MIF promoted anchorage-independent growth and inhibited apoptosis of human adenoma cells in vitro.
- MIF deletion reduced tumor number/size and angiogenesis in ApcMin/+ mice, without affecting cell apoptosis or proliferation.
Conclusions:
- MIF expression increases in human colorectal adenomas.
- MIF promotes intestinal tumorigenesis, primarily through angiogenesis.
- MIF represents a potential therapeutic target for colorectal cancer chemoprevention.
