Vasculogenic mimicry (VM) is different from classical tumor angiogenesis and does not depend on endothelial cells. VM is closely related to the prognosis of various cancers. Canstatin was first identified as an endogenous angiogenesis inhibitor. In the present study, the inhibitory effect of canstatin on VM formation was evaluated. Human glioblastoma cell lines U87 and U251 were letivirally transduced to overexpress canstatin gene or GFP as control. In vitro assays showed that canstatin overexpression reduced the tube formation of U87 and U251 cells in Matrigel. A xenograft glioma model was created by subcutaneous injection of lentivirally modified U87 cells into nude mice. The results of in vivo experiments showed that canstatin gene introduction inhibited the growth of glioma xenografts. In tumor xenografts overexpressing canstatin, U87-mediated formation of VM-like structures and VM-related VEGF (vascular endothelial growth factor) expression were remarkably reduced. Canstatin overexpression also decreased the phosphorylation of Akt and reduced the expression of Survivin in vitro. In addition, HIF-1α production and MMP-2 secretion were decreased by canstatin overexpression. Therefore, these results suggested a protective role of canstatin during VM-like structure formation of glioma probably via inhibiting signaling pathways inducing vasculogenic mimicry.

中文翻译：

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Canstatin 通过抑制 VM 样结构的形成来抑制神经胶质瘤的生长。

血管生成拟态 (VM) 不同于经典的肿瘤血管生成，并且不依赖于内皮细胞。VM与各种癌症的预后密切相关。卡斯达汀首先被鉴定为内源性血管生成抑制剂。在本研究中，评估了卡斯达汀对 VM 形成的抑制作用。人胶质母细胞瘤细胞系 U87 和 U251 被慢病毒转导以过表达 canstatin 基因或 GFP 作为对照。体外测定表明，canstatin 过表达减少了 Matrigel 中 U87 和 U251 细胞的管形成。通过将慢病毒修饰的 U87 细胞皮下注射到裸鼠中来创建异种移植胶质瘤模型。体内实验结果表明，canstatin 基因导入抑制了胶质瘤异种移植物的生长。在过表达 canstatin 的肿瘤异种移植物中，U87 介导的 VM 样结构的形成和 VM 相关的 VEGF（血管内皮生长因子）表达显着降低。在体外，Canstatin 过表达也降低了 Akt 的磷酸化并降低了 Survivin 的表达。此外，卡斯达汀过表达降低了 HIF-1α 的产生和 MMP-2 的分泌。因此，这些结果表明卡斯达汀在胶质瘤的 VM 样结构形成过程中的保护作用可能是通过抑制诱导血管生成拟态的信号通路。卡斯达汀过表达降低了 HIF-1α 的产生和 MMP-2 的分泌。因此，这些结果表明卡斯达汀在胶质瘤的 VM 样结构形成过程中具有保护作用，可能是通过抑制诱导血管生成拟态的信号通路。卡斯达汀过表达降低了 HIF-1α 的产生和 MMP-2 的分泌。因此，这些结果表明卡斯达汀在胶质瘤的 VM 样结构形成过程中的保护作用可能是通过抑制诱导血管生成拟态的信号通路。