title: Macrophage migration inhibitory factor increases cell motility and up-regulates αvβ3 integrin in human chondrosarcoma cells.
abstract: The macrophage migration-inhibitory factor (MIF) is a pro-inflammatory cytokine first known for its effect on macrophage migration and activation. Recent studies have shown that MIP plays a critical role in tumor growth, angiogenesis, and metastasis. Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. However, the effects of MIF on human chondrosarcoma cells are largely unknown. In the present study, MIF was found to increase the migration and the expression of αvβ3 integrin in human chondrosarcoma cells. The phosphatidylinositol 3-kinase (PI3K), Akt, and NF-κB pathways were activated by MIF treatment, and the MIF-induced expression of integrin and migration activity were inhibited by the specific inhibitors and mutant forms of PI3K, Akt, and NF-κB cascades. In addition, migration-prone sublines demonstrated that increased cell migration ability was correlated with increased expression of MIF and αvβ3 integrin. Taken together, our results indicate that MIF enhanced the migration of the chondrosarcoma cells by increasing αvβ3 integrin expression through the PI3K/Akt/NF-κB signal transduction pathway.
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Chun-Yi
authors.initials: CY
authors.lastname: Lee
authors.forename: Mei-Ju
authors.initials: MJ
authors.lastname: Su
authors.forename: Chun-Yin
authors.initials: CY
authors.lastname: Huang
authors.forename: Meng-Yi
authors.initials: MY
authors.lastname: Chen
authors.forename: Horng-Chaung
authors.initials: HC
authors.lastname: Hsu
authors.forename: Ching-Yuang
authors.initials: CY
authors.lastname: Lin
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002813:Chondrosarcoma / Q000235:genetics / Q000503:physiopathology*; D055785:Gene Knockdown Techniques; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D039302:Integrin alphaVbeta3; D008263:Macrophage Migration-Inhibitory Factors; D016328:NF-kappa B; D000081082:Phosphoinositide-3 Kinase Inhibitors; D034741:RNA, Small Interfering; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt