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

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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.