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 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.
Li
Ying-Ying
YY
Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung & Chang Gung University, Taiwan.
Hsieh
Ling-Ling
LL
Tang
Rei-Ping
RP
Liao
Shuen-Keui
SK
Yeh
Kun-Yun
KY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001483:Base Sequence; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism*; D055262:Mucin-2 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000737:chemistry / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry; D015854:Up-Regulation; D000093242:Interleukin-6 Inhibitors; D000097382:CD68 Molecule
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017931:DNA Primers; D015850:Interleukin-6; D018396:Mucin-1; D055262:Mucin-2; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; D014443:Tyrosine; D000093242:Interleukin-6 Inhibitors; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C508600:IL6 protein, human; C060192:MUC1 protein, human; C524625:MUC2 protein, human; C494086:STAT3 protein, human