B7-H6 expression is induced by lipopolysaccharide and facilitates cancer invasion and metastasis in human gliomas.

Although great progress has been made in treatment regimens, gliomas are still incurable and the 5-year survival remains poor. Studies focusing on molecules that regulate tumorigenesis or tumor immunity may provide potential therapeutic strategies for patients with glioma. B7-H6 is selectively expressed in tumor cells and plays vital roles in host immune responses. In this study, we demonstrated that B7-H6 was expressed in glioma cell lines, including CRT, U251, SHG-44, SF-295, TG-905 and U373, and tumor tissues isolated from glioma patients. Moreover, the expression levels of B7-H6 were significantly correlated with glioma grade. Previous studies reported that inflammatory mediators and cytokines induced the expression of B7 family members including programmed death-ligand 1, B7-H2 and B7-H4. Therefore, we explored the regulation of B7-H6 expression in gliomas and showed that lipopolysaccharide induced the expression of B7-H6 in glioma cells. To further analyze the roles of B7-H6 in gliomas, the expression of B7-H6 in glioma cells was knocked down. The results of cell counting kit-8, colony formation, wound healing, and transwell migration and invasion assays demonstrated that the proliferation, migration and invasion of glioma cells were inhibited after knocking down B7-H6. To elucidate the specific mechanisms of B7-H6 function in cancer progression, we examined the expression levels of proteins involved in cell apoptosis, migration and invasion. We demonstrated that the expression levels of E-cadherin and Bcl-2 associated X protein increased, and the expression levels of vimentin, N-cadherin, matrix metalloproteinase-2, matrix metalloproteinase-9 and survivin decreased after knocking down B7-H6. In conclusion, B7-H6 plays important roles in glioma, and targeting B7-H6 may provide a novel therapeutic strategy for glioma patients.