Activation of macrophages by mucins produced from epithelial cancer cells and its effect

我们发现，上皮性癌细胞产生的粘蛋白激活了单核/巨噬细胞。单核细胞与粘蛋白孵育后产生IL-1、β和PGE_2等细胞因子，其合成呈剂量依赖性增加。环氧合酶2(COX2)是PGE2生物合成的限速酶。结果表明，粘蛋白可诱导COX2mRNA和酶蛋白表达。我们还用免疫组织化学方法检测了COX2蛋白和粘蛋白在人结直肠癌组织中的定位。值得注意的是，表达COX2的巨噬细胞位于可检测到粘蛋白的区域周围。接下来，我们使用小鼠乳腺肿瘤细胞系TA3-Ha和TA3-St观察了肿瘤组织的形成。众所周知，前者会产生名为表观粘蛋白的粘蛋白，而后者则不会。尽管两种细胞在体外的生长速度相似，但前者在体内形成肿瘤组织的速度要比后者快得多。免疫组织化学显示，前者可见巨噬细胞COX2的诱导，后者未见。这些结果表明，粘蛋白对COX2的诱导在肿瘤的形成中起重要作用。

We found that mucins produced by epithelial cancer cells activated monocytes/macrophages. Monocytes incubated with mucins produced cytokines such as IL-1β and PGE2, which synthesis was elevated in a dose-dependent manner. Cyclooxygenase 2 (COX2) is a rate-limiting enzyme for biosynthesis of PGE2. It is noted that COX2 mRNA and enzyme protein were induced by mucins. We also examined immunohistochemically the localization of COX2 protein and mucins in human colorectal cancer tissues. It is noteworthy that COX2-expressing macrophages were located around the region in which mucins were detectable.Next, we examined the formation of cancer tissues using a mouse mammary tumor cell line, TA3-Ha and TA3-St. It is known that the former produces mucins named epiglycanin, but the latter does not. Although both cells grew at the similar rate in vitro, the former formed the cancer tissues much more rapidly than the latter in vivo. Induction of COX2 of infiltrated macrophages could be observed in the former tissues immunohistochemically but not in the latter. These results indicate that the induction of COX2 by mucins plays a significant role in the tumor formation.