ABSTRACT
Chemokine receptor 7 (CCR7) has emerged as an inducer of invasion, migration, and epithelial-mesenchymal transition (EMT) in cancer. In this research, human malignant glioma cells were stimulated with transforming growth factor beta 1 (TGF-ß1) and siCCR7. The data show that CCR7 mediates TGF-ß1-induced EMT, migration, and invasion in U251 and U87 cells and that these effects of TGF-ß1 were reversed by treatment with siCCR7 or a CCR7 neutralizing antibody. Importantly, the TGF-ß1-mediated increase in nuclear factor kappaB (NF-κB) activity in human glioma cells was reduced by treatment with siCCR7 or a CCR7 neutralizing antibody. Furthermore, CCR7 was shown to mediate TGF-ß1-induced glioma cancer cell migration by activating matrix metalloproteinase 2 (MMP2)/9. Our results indicate that CCR7 mediates TGF-ß1-induced MMP2/9 expression through NF-κB signaling, thus facilitating glioma cell migration, invasion, and EMT, all of which progressively increase with glioblastoma progression. These findings indicate that CCR7 is a potential therapeutic target for malignant glioma.
