Wang Ting-Chung, Luo Sheng-Jie, Chang Shun-Fu
Department of Neurosurgery, Chiayi Chang Gung Memorial Hospital, Chiayi 613, Taiwan.
School of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Life (Basel). 2021 Jul 17;11(7):708. doi: 10.3390/life11070708.
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.
胶质母细胞瘤，世界卫生组织IV级，是最恶性的胶质瘤类型，由于高度异质性和无法控制的转移特性，它仍然是一种无法治愈的肿瘤。除了具有抑制肿瘤发生的活性外，骨形态发生蛋白7（BMP7）最近还被发现其在胶质母细胞瘤中具有促进侵袭的作用。然而，这个问题的详细和精确机制仍有待进一步阐明。因此，在本研究中，我们确定了BMP7对胶质母细胞瘤迁移和迁移调节的影响及其潜在机制。本研究使用了人LN18/LN229胶质母细胞瘤细胞。我们的结果显示，与健康脑组织相比，人恶性胶质瘤组织中BMP7/pSmad5水平更高。此外，研究表明内源性和外源性BMP7刺激均可增加人LN18/LN229胶质母细胞瘤细胞的迁移和侵袭能力。而且，这一过程受Smad5和p75神经营养因子受体（p75NTR）信号通路调节。此外，意外的数据是，Smad1基因敲低可导致人LN18胶质母细胞瘤细胞死亡。总体而言，本研究发现BMP7的促侵袭活性可能是胶质母细胞瘤的一种自分泌刺激，且这种作用可由Smad5-p75NTR信号通路调节。
