| First Author | Cheon EC | Year | 2012 |
| Journal | J Gastrointest Surg | Volume | 16 |
| Issue | 2 | Pages | 389-93 |
| PubMed ID | 22072302 | Mgi Jnum | J:321173 |
| Mgi Id | MGI:6883958 | Doi | 10.1007/s11605-011-1761-x |
| Citation | Cheon EC, et al. (2012) Genetic deletion of 5-lipoxygenase increases tumor-infiltrating macrophages in Apc(Delta468) mice. J Gastrointest Surg 16(2):389-93 |
| abstractText | 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(Delta468) 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 beta-hexosaminidase release, respectively. RESULTS: APC(Delta468)/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. |
