背景:胶质母细胞瘤,成人最常见的原发性恶性脑肿瘤,是一种以异常血管生成为特征的高度血管化肿瘤。在胶质母细胞瘤中也报道了肿瘤血管化的其他机制,包括通过血管生成拟态(VM)形成肿瘤细胞衍生的血管或肿瘤细胞向内皮细胞的转分化。VM和内皮转分化经常被报道为不同的过程,然而,同时使用这两个术语来描述单一的血管化过程.在识别每个过程时,也报告了一些重叠的特征。因此,我们旨在确定胶质母细胞瘤文献中始终归因于VM和内皮转分化的标志物。
方法:搜索了OvidMEDLINE和OvidEmbase在1999年1月至2021年7月之间发表的评估人胶质母细胞瘤中VM或肿瘤向内皮转分化的研究。在线系统评价工具Covidence用于筛选和数据提取。提取的数据包括报告的肿瘤来源的脉管系统的类型,使用的方法和技术,和被调查的标记。根据报告的脉管系统类型对研究进行分组以进行进一步评估。
结果:在确定的419条独特记录中,有113条被纳入分析。VM在64/113研究中报告,而肿瘤向内皮转分化在16/113研究中报道。其余的研究使用这两个术语来描述一个单一的过程,没有定义发生的过程,或得出结论,既没有VM也没有内皮转分化发生。血管结构中CD34和/或CD31的缺失是VM最常见的指标,而CD34和/或CD31的表达,除了各种其他内皮细胞,干细胞或肿瘤细胞标志物,提示肿瘤向内皮转分化。
结论:源自肿瘤向内皮转分化的细胞表达典型的内皮标志物,包括CD34和CD31,而促成VM的肿瘤细胞缺乏CD34和CD31表达。需要额外的肿瘤标志物来识别胶质母细胞瘤组织中的转分化,这个过程需要进一步的表征。
BACKGROUND: Glioblastoma, the most common primary malignant brain tumour in adults, is a highly vascular tumour characterised by abnormal angiogenesis. Additional mechanisms of tumour vascularisation have also been reported in glioblastoma, including the formation of tumour cell-derived vessels by vasculogenic mimicry (VM) or the transdifferentiation of tumour cells to endothelial cells. VM and endothelial
transdifferentiation have frequently been reported as distinct processes, however, the use of both terms to describe a single process of vascularisation also occurs. Some overlapping characteristics have also been reported when identifying each process. We therefore aimed to determine the markers consistently attributed to VM and endothelial transdifferentiation in the glioblastoma literature.
METHODS: Ovid MEDLINE and Ovid Embase were searched for studies published between January 1999 and July 2021 that assessed VM or tumour to endothelial transdifferentiation in human glioblastoma. The online systematic
review tool Covidence was used for screening and data extraction. Extracted data included type of tumour-derived vasculature reported, methods and techniques used, and markers investigated. Studies were grouped based on type of vasculature reported for further assessment.
RESULTS: One hundred and thirteen of the 419 unique records identified were included for analysis. VM was reported in 64/113 studies, while tumour to endothelial
transdifferentiation was reported in 16/113 studies. The remaining studies used both terms to describe a single process, did not define the process that occurred, or concluded that neither VM nor endothelial transdifferentiation occurred. Absence of CD34 and/or CD31 in vascular structures was the most common indicator of VM, while expression of CD34 and/or CD31, in addition to various other endothelial, stem cell or tumour cell markers, indicated tumour to endothelial transdifferentiation.
CONCLUSIONS: Cells derived from tumour to endothelial
transdifferentiation express typical endothelial markers including CD34 and CD31, while tumour cells contributing to VM lack CD34 and CD31 expression. Additional tumour markers are required to identify
transdifferentiation in glioblastoma tissue, and this process requires further characterisation.