A protective role of mast cells in intestinal tumorigenesis
A protective role of mast cells in intestinal tumorigenesis
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DOI：
10.1093/carcin/bgn040
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发表时间：
2008-04-01
期刊：
影响因子：
4.7
通讯作者：
Matrisian, Lynn M.
中科院分区：
文献类型：
--
作者：
Sinnamon, Mark J.;Carter, Kathy J.;Matrisian, Lynn M.
肥大细胞在许多类型的肿瘤中被观察到;然而，它们在癌发生中的作用仍然知之甚少。大多数流行病学证据表明，乳腺、肺和结肠肿瘤中肥大细胞的存在与肿瘤进展之间存在负相关。多发性肠肿瘤（Min，AP（Min/+））小鼠中的肠腺瘤显示肥大细胞数量增加和肥大细胞相关蛋白酶丰度增加，如通过用Hu/Mu ProtIn微阵列的转录谱测定的。为了研究肥大细胞在肠肿瘤发生中的作用，将肥大细胞缺陷的突变小鼠系Sash小鼠（c-ki（W-sh/W-sh））与Min小鼠（肠肿瘤的遗传模型）杂交。由此产生的肥大细胞缺陷型Min-Sash小鼠比同窝对照组多产生50%的腺瘤，并且Min-Sash小鼠中的肿瘤大33%。肥大细胞缺陷并不影响肿瘤细胞增殖，但是，肥大细胞缺陷小鼠的细胞凋亡被显着抑制。肥大细胞已被证明是许多炎症细胞的关键上游调节因子。Min和Min-Sash小鼠之间的中性粒细胞、巨噬细胞和T细胞群相似;然而，从Min-Sash动物获得的肿瘤中的嗜酸性粒细胞显著较少。这些结果表明肥大细胞在早期肠道肿瘤发生的遗传模型中具有保护性抗肿瘤作用。
Mast cells have been observed in numerous types of tumors; however, their role in carcinogenesis remains poorly understood. The majority of epidemiological evidence suggests a negative association between the presence of mast cells and tumor progression in breast, lung and colonic neoplasms. Intestinal adenomas in the multiple intestinal neoplasia (Min, AP(Min/+)) mouse displayed increased numbers of mast cells and increased abundance of mast cell-associated proteinases as determined by transcriptional profiling with the Hu/Mu ProtIn microarray. To examine the role of mast cells in intestinal tumorigenesis, a mutant mouse line deficient in mast cells, Sash mice (c-ki(W-sh/W-sh)) was crossed with the Min mouse, a genetic model of intestinal neoplasia. The resulting mast cell-deficient Min-Sash mice developed 50% more adenomas than littermate controls and the tumors were 33% larger in Min-Sash mice. Mast cell deficiency did not affect tumor cell proliferation; however, apoptosis was significantly inhibited in mast cell-deficient mice. Mast cells have been shown to act as critical upstream regulators of numerous inflammatory cells. Neutrophil, macrophage and T cell populations were similar between Min and Min-Sash mice; however, eosinophils were significantly less abundant in tumors obtained from Min-Sash animals. These results indicate a protective, antitumor role of mast cells in a genetic model of early-stage intestinal tumorigenesis.