Bone Morphogenetic Protein 7 Effect on Human Glioblastoma Cell Transmigration and Migration

Abstract

Glioblastoma, World Health Organization—grade IV, is the most malignant glioma type and it is still an incurable tumor due to the high level of heterogeneity and uncontrolled metastatic nature. In addition to the tumorigenicity-suppressing activity, bone morphogenetic protein 7 (BMP7) has recently been found for its invasion-promoting role in glioblastoma. However, the detailed and precise mechanism in this issue should have more elucidation. Thus, in this study, we determined the BMP7 effect on glioblastoma transmigration and migration regulations and the underlying mechanisms. Human LN18/LN229 glioblastoma cells were used in this study. Our results showed a higher BMP7/pSmad5 level in human malignant glioma tissues compared to healthy brain tissues. In addition, it was demonstrated that endogenous and exogenous BMP7 stimulation could increase the transmigration and migration capabilities of human LN18/LN229 glioblastoma cells. Moreover, this event is regulated by Smad5 and p75 neurotrophin receptor (p75NTR) signaling. Furthermore, unexpected data are that the Smad1 gene knockdown could lead to the cell death of human LN18 glioblastoma cells. Overall, the present study finds that the invasion-promoting activity of BMP7 might be an autocrine stimulation of glioblastoma and this effect could be regulated by Smad5-p75NTR signaling.