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.
Highlights
Glioma is still a most malignant tumor of brain due to its extremely high invasion and diffusion properties [1,2,3]
We investigated the potential role of bone morphogenetic protein 7 (BMP7) in glioblastoma cell transmigration and migration capabilities
In this BMP7 event, we further demonstrated that p75 neurotrophin receptor (p75NTR) could be upregulated in glioblastoma cells by Smad5 signaling
Summary
Glioma is still a most malignant tumor of brain due to its extremely high invasion and diffusion properties [1,2,3]. In most of the studies, BMP7 has been elucidated an antiproliferation and anti-survival role in glioma by its growth inhibitory and differentiation inducer activity [12,13,14,15]. We investigated the potential role of BMP7 in glioblastoma cell transmigration and migration capabilities. We found a higher BMP7/pSmad level in clinical malignant glioma and found an autocrine effect of BMP7 on glioblastoma cell transmigration and migration. In this BMP7 event, we further demonstrated that p75NTR could be upregulated in glioblastoma cells by Smad signaling. Our findings provide new insights into the understanding and elucidation of autocrine role of BMP7 and Smad1/5 signaling in promoting the glioblastoma metastasis
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