Genetic Deletion of 5-Lipoxygenase Increases Tumor-Infiltrating Macrophages in Apc Δ468 Mice

Eric C. Cheon, Matthew J. Strouch, Seth B. Krantz, Michael J. Heiferman, David J. Bentrem

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Introduction: The role of 5-lipoxygenase (5-LO) in colon cancer is unknown. Tumor-infiltrating macrophages, neutrophils, and mast cells have been shown to play important roles in colon tumorigenesis and are dependent on 5-LO for function. Methods and Materials: Utilizing the APC Δ468 polyposis model, we performed 5-LO gene knockouts and evaluated the subsequent changes in macrophage, neutrophil, and mast cell density at the tumor site. The proliferative and degranulation capacities of 5-LO-deficient mast cells were also measured, quantifying thymidine incorporation and β-hexosaminidase release, respectively. Results: APC Δ468/5LO -/- mice displayed increased tumor-infiltrating macrophages and decreased neutrophils at the polyp site. In vitro, mast cells deficient for 5-LO proliferated at a diminished rate while mast cell degranulation was unchanged. Discussion: We provide evidence suggesting that 5-LO deficiency has differential effects on the infiltration of macrophages and neutrophils in adenomatous polyps, increasing and decreasing infiltration of these cells, respectively. Our observations are consistent with a protective role for tumor-infiltrating macrophages in the initiation of polyp formation. The mechanisms through which 5-LO deficiency negatively affects these cells are under investigation. Conclusions: These results provide evidence that 5-LO plays an important role in tumorigenesis and further indicate that 5-LO-selective inhibitors can be investigated as potential therapeutic agents for colorectal polyposis and cancer.

Original languageEnglish (US)
Pages (from-to)389-393
Number of pages5
JournalJournal of Gastrointestinal Surgery
Volume16
Issue number2
DOIs
Publication statusPublished - Feb 1 2012

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Keywords

  • 5-Lipoxygenase
  • Colon cancer
  • Macrophage
  • Mast cell
  • Polyp

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology

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