Macrophage-derived interleukin-6 up-regulates MUC1, but down-regulates MUC2 expression in the human colon cancer HT-29 cell line

Little is known regarding the effects of IL-6 released by tumor-infiltrating macrophages on the mucin expression of colon cancer cells. We isolated macrophages from healthy donors and harvested the supernatant after 48-h cultures. Using flow cytometry and intracellular staining methods, we found that macrophage supernatant effectively induced MUC1 up-regulation and MUC2 down-regulation of colon cancer cells in vitro. Western blotting analysis using monoclonal antibody against IL-6 or gp 130 verified that this IL-6-driven activity was through the activation of tyrosine phosphorylation (Tyr705) of STAT3 in cancer cells. We analyzed the surgical specimens of 29 patients with colon cancer by an immunohistochemical staining method and demonstrated the co-localization of macrophages, and the expression of IL-6, CD68, and MUC1 in colon cancer patients. Therefore, macrophage-derived IL-6 modulates the mucin expression of colorectal cancer cells that might in turn produce a permissive milieu favorable to cancer spread.