Genetic Deletion of 5-Lipoxygenase Increases Tumor-Infiltrating Macrophages in ApcΔ468 Mice
Genetic Deletion of 5-Lipoxygenase Increases Tumor-Infiltrating Macrophages in ApcΔ468 Mice
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DOI：
10.1007/s11605-011-1761-x
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发表时间：
2012-02-01
影响因子：
3.2
通讯作者：
Bentrem, David J.
中科院分区：
文献类型：
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作者：
Cheon, Eric C.;Strouch, Matthew J.;Bentrem, David J.
5-脂氧合酶（5-LO）在结肠癌中的作用尚不清楚。肿瘤浸润的巨噬细胞，中性粒细胞和肥大细胞已被证明在结肠肿瘤发生中发挥重要作用，并依赖于5-LO的function.Methods和材料利用APC（德尔塔468）息肉病模型，我们进行了5-LO基因敲除，并评估了随后的变化，巨噬细胞，中性粒细胞和肥大细胞密度在肿瘤部位。结果APC（Delta 468）/5LO（-/-）小鼠息肉部位肿瘤浸润巨噬细胞增多，嗜中性粒细胞减少。在体外，肥大细胞5-LO缺乏增殖率下降，而肥大细胞脱颗粒是unchanged.Discussion我们提供的证据表明，5-LO缺乏有差异的影响，巨噬细胞和中性粒细胞的浸润，腺瘤性息肉，增加和减少这些细胞的浸润，分别。我们的观察结果与肿瘤浸润性巨噬细胞在息肉形成的起始中的保护作用一致。通过5-LO缺陷负面影响这些cells的机制正在调查中。结论这些结果提供了证据，5-LO在肿瘤发生中起着重要作用，并进一步表明，5-LO选择性抑制剂可以作为潜在的治疗剂，结肠直肠息肉病和癌症的研究。
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(Delta 468) 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(Delta 468)/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.