Han Guosheng, Li Yanan, Cao Yiqun, Yue Zhijian, Zhang Yuhui, Wang Laixing, Liu Jianmin
Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
Oncotarget. 2017 Apr 21;8(35):58163-58171. doi: 10.18632/oncotarget.17344. eCollection 2017 Aug 29.
Vasculogenic mimicry (VM) was an important tumor blood supply to complement the endothelial cell-dependent angiogenesis, while leptin and receptor (ObR) involved in angiogenesis in glioblastoma has been reported on previous study, but the relationship between ObR expression and VM formation in human glioblastoma tissues, as well as their prognostic significance still remains unclear. In our study, we found that VM recognized by CD31-/PAS+ immunohistochemical staining in glioblastoma tissues showed a positive correlation with leptin expression ( = 0.58, < 0.01), as well as ObR expression in glioblastoma tissues ( = 0.61, < 0.01). Association of glial to mesenchymal transition (GMT)-related molecular with ObR expression and VM formation in glioblastoma tissues indicated that ObR-positive glioblastoma cells with GMT phenotype might be more likely to constitute VM, and co-expression of ObR and CD133 or Nestin to constitute the channel impliated that ObR-positive glioblastoma cells displayed glioblastoma stem cells (GSC) properties. Moreover, Kaplan-Meier statistical analysis showed that patients with more VM or ObR expression displayed poorer prognosis for overall survival times than patients with less expression (VM vs. VM: = 0.033; ObR vs. ObR: = 0.009). And ObR+ glioblastoma cells with GSC characteristic were mostly involved in VM formation, whereas a little part of cells were also related to microvascular density (MVD), which suggested that ObR was an important target for anticancer therapy, so further related studies were needed to improve glioblastoma treatment.
血管生成拟态（VM）是一种重要的肿瘤血液供应方式，可补充依赖内皮细胞的血管生成，先前的研究报道了瘦素及其受体（ObR）参与胶质母细胞瘤的血管生成，但在人胶质母细胞瘤组织中ObR表达与VM形成之间的关系及其预后意义仍不清楚。在我们的研究中，我们发现胶质母细胞瘤组织中通过CD31-/PAS+免疫组化染色识别的VM与瘦素表达呈正相关（r = 0.58，P < 0.01），也与胶质母细胞瘤组织中的ObR表达呈正相关（r = 0.61，P < 0.01）。胶质母细胞瘤组织中神经胶质向间充质转化（GMT）相关分子与ObR表达及VM形成的相关性表明，具有GMT表型的ObR阳性胶质母细胞瘤细胞可能更易构成VM，ObR与CD133或巢蛋白共表达构成通道提示ObR阳性胶质母细胞瘤细胞具有胶质母细胞瘤干细胞（GSC）特性。此外，Kaplan-Meier统计分析显示，VM或ObR表达较多的患者总生存时间的预后比表达较少的患者差（VM vs. VM：P = 0.033；ObR vs. ObR：P = 0.009）。具有GSC特征的ObR+胶质母细胞瘤细胞大多参与VM形成，而一小部分细胞也与微血管密度（MVD）有关，这表明ObR是抗癌治疗的重要靶点，因此需要进一步开展相关研究以改善胶质母细胞瘤的治疗。
