Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
J Cell Biochem. 2012 May;113(5):1590-8. doi: 10.1002/jcb.24027.
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.
巨噬细胞移动抑制因子（MIF）是一种前炎症细胞因子，最初因其对巨噬细胞迁移和激活的影响而被人们所熟知。最近的研究表明，MIF 在肿瘤生长、血管生成和转移中发挥着关键作用。软骨肉瘤是一种高度恶性的肿瘤，具有很强的局部侵袭和远处转移的能力。然而，MIF 对人软骨肉瘤细胞的影响在很大程度上尚不清楚。在本研究中，发现 MIF 可增加人软骨肉瘤细胞的迁移和αvβ3 整合素的表达。MIF 处理激活了磷脂酰肌醇 3-激酶（PI3K）、Akt 和 NF-κB 通路，PI3K、Akt 和 NF-κB 级联的特异性抑制剂和突变体抑制了整合素的表达和迁移活性。此外，迁移倾向的亚系表明，细胞迁移能力的增加与 MIF 和αvβ3 整合素表达的增加相关。总之，我们的研究结果表明，MIF 通过增加 PI3K/Akt/NF-κB 信号转导通路中αvβ3 整合素的表达，增强了软骨肉瘤细胞的迁移能力。
