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

我们发现上皮癌细胞产生的粘蛋白激活了单核细胞/巨噬细胞。与粘蛋白孵育的单核细胞产生细胞因子，如IL-1β和PGE2，其合成以剂量依赖性方式升高。环氧合酶2 （COX2）是生物合成PGE2的限速酶。我们注意到粘蛋白诱导了COX2 mRNA和酶蛋白的表达。我们也用免疫组织化学方法检测了COX2蛋白和粘蛋白在人类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检测癌组织的形成。众所周知，前者会产生一种叫做表胰甘肽的黏素，而后者则不会。尽管两种细胞在体外的生长速度相似，但前者在体内形成癌组织的速度要比后者快得多。免疫组化观察到前一种组织中浸润的巨噬细胞诱导COX2，后一种组织中没有。这些结果表明粘蛋白诱导COX2在肿瘤形成中起重要作用。

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.