title: IL-6 increases MMP-13 expression and motility in human chondrosarcoma cells.
abstract: Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. IL-6 is a multifunctional cytokine that is associated with the disease status and outcomes of cancers. However, the effect of IL-6 on the migration activity of human chondrosarcoma cells is mostly unknown. Here, we found that IL-6 increased the migration and expression of MMP-13 in human chondrosarcoma cells. We also found that human chondrosarcoma tissues had significant expression of IL-6, which was higher than that in normal cartilage. IL-6-mediated migration and MMP-13 up-regulation were attenuated by anti-IL-6 receptor antibody, Ras, Raf-1, and a MEK inhibitor. Activation of the Ras, Raf-1, MEK, ERK, and NF-κB signaling pathways after IL-6 treatment was demonstrated, and IL-6-induced MMP-13 expression and migration activity were inhibited by the specific inhibitor and mutant Ras, Raf-1, MEK, ERK, and NF-κB cascades. In addition, migration-prone sublines demonstrated that cells with increasing migration ability had greater expression of IL-6 and MMP-13. Taken together, these results indicate that IL-6 and IL-6 receptor interaction enhances migration of chondrosarcoma through an increase in MMP-13 production.
authors.affiliation: Department of Pharmacology, School of Medicine, China Medical University and Hospital, Taichung 404, Taiwan. chtang@mail.cmu.edu.tw
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
authors.forename: Cheng-Fong
authors.initials: CF
authors.lastname: Chen
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Chen
authors.forename: Yi-Chin
authors.initials: YC
authors.lastname: Fong
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D002813:Chondrosarcoma / Q000378:metabolism* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism* / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism* / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D016328:NF-kappa B; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D053509:Matrix Metalloproteinase 13