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 (Tyr(705)) of STAT3 in cancer cells. We analyzed the surgical specimens of 29 patients with colon cancer by an immunohistochemical mica I 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. (C) 2009 Elsevier Inc. All rights reserved.