title: CCL2 increases MMP-9 expression and cell motility in human chondrosarcoma cells via the Ras/Raf/MEK/ERK/NF-κB signaling pathway.
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. Chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1 (MCP-1), belongs to the CC chemokine family that is associated with the disease status and outcomes of cancers. However, the effect of CCL2 on migration activity in human chondrosarcoma cells is mostly unknown. Here we found that CCL2 increased the migration and expression of matrix metalloproteinase (MMP)-9 in human chondrosarcoma cells. CCL2-mediated migration and MMP-9 up-regulation were attenuated by CCR2, Ras, Raf-1, and MEK inhibitor. Activation of the Ras, Raf-1, MEK, ERK, and NF-κB signaling pathway after CCL2 treatment was demonstrated, and CCL2-induced expression of MMP-9 and migration activity were inhibited by the specific inhibitor, and mutant of Ras, Raf-1, MEK, ERK, and NF-κB cascades. Taken together, our results indicated that CCL2 enhances the migration of chondrosarcoma cells by increasing MMP-9 expression through the CCR2 receptor, Ras, Raf-1, MEK, ERK, and NF-κB signal transduction pathway.
authors.affiliation: Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan. chtang@mail.cmu.edu.tw
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
authors.forename: Chia-Chun
authors.initials: CC
authors.lastname: Tsai
mesh_terms: D001859:Bone Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D018932:Chemokine CCL2 / Q000502:physiology*; D002813:Chondrosarcoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D016328:NF-kappa B / Q000502:physiology*; D019908:Proto-Oncogene Proteins c-raf / Q000502:physiology; D054390:Receptors, CCR2 / Q000502:physiology; D018631:ras Proteins / Q000502:physiology*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016328:NF-kappa B; D054390:Receptors, CCR2; D019908:Proto-Oncogene Proteins c-raf; D020780:Matrix Metalloproteinase 9; D018631:ras Proteins