分泌性脑膜趋化因子而非 VEGFA 调节髓母细胞瘤细胞的迁移特性。
Secreted meningeal chemokines, but not VEGFA, modulate the migratory properties of medulloblastoma cells.
机构信息
Pediatric Cancer Biology Program, Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.
Pediatric Cancer Biology Program, Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.
出版信息
Biochem Biophys Res Commun. 2014 Jul 18;450(1):555-60. doi: 10.1016/j.bbrc.2014.06.018. Epub 2014 Jun 10.
Leptomeningeal metastasis is a cause of morbidity and mortality in medulloblastoma, but the understanding of molecular mechanisms driving this process is nascent. In this study, we examined the secretory chemokine profile of medulloblastoma cells (DAOY) and a meningothelial cell line (BMEN1). Conditioned media (CM) of meningothelial cells increased adhesion, spreading and migration of medulloblastoma. VEGFA was identified at elevated levels in the CM from BMEN1 cells (as compared to DAOY CM); however, recombinant VEGFA alone was insufficient to enhance medulloblastoma cell migration. In addition, bevacizumab, the VEGFA scavenging monoclonal antibody, did not block the migratory phenotype induced by the CM. These results reveal that paracrine factors secreted by meningothelial cells can influence migration and adherence of medulloblastoma tumor cells, but VEGFA may not be a specific target for therapeutic intervention in this context.
脑膜转移是髓母细胞瘤发病和死亡的一个原因，但对驱动这一过程的分子机制的了解还处于起步阶段。在这项研究中，我们研究了髓母细胞瘤细胞（DAOY）和脑膜内皮细胞系（BMEN1）的分泌趋化因子谱。脑膜内皮细胞的条件培养基（CM）增加了髓母细胞瘤的黏附、铺展和迁移。与 DAOY CM 相比，BMEN1 细胞 CM 中 VEGFA 的水平升高；然而，单独的重组 VEGFA 不足以增强髓母细胞瘤细胞的迁移。此外，VEGFA 清除单克隆抗体 bevacizumab 并不能阻断 CM 诱导的迁移表型。这些结果表明，脑膜内皮细胞分泌的旁分泌因子可以影响髓母细胞瘤肿瘤细胞的迁移和黏附，但 VEGFA 可能不是这种情况下治疗干预的特定靶点。
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