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[人胶质瘤新生血管形成的细胞来源及其功能评价的初步研究]

[Preliminary studies on cell derivation of neovascularization in human glioma and its functional evaluation].

作者信息

Fei Xi-feng, Zhang Quan-bin, Dong Jun, Wang Ai-dong, Wang Zhi-min, Huang Qiang

机构信息

Department of Neurosurgery, Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou 215021, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2011 Oct;33(10):726-31.

Abstract

OBJECTIVE

The finding of vasculogenic mimicry (VM) in many solid tumors indicates that tumor cells themselves could participate in the construction of tumor vessels. However the origin of these cells is still not fully elucidated, and whether these vessels have the ability of blood-supply is still unclear. Preliminary studies were performed to investigate whether part of tumor neovascularity is derived from tumor stem cells (TSCs) and whether TSCs-derived vessels are functional.

METHODS

Transplanted glioma tissues obtained from subcutaneous and orthotopic transplantation nude mouse models were processed into paraffin sections. In order to identify the cell origin and types of tumor vessels, sections were stained with CD31, CD34, CD133, GFAP, Ki67 and HLA, respectively. CD34-PAS staining was performed as well. A part of tumor-bearing mice were perfused with activated carbon through the systemic circulation and the distribution of activated carbon was observed.

RESULTS

CD34-PAS staining showed that endothelium-dependent vessels (CD34(+), PAS(+)), VM vessels (CD34(-), PAS(+)), and the MVs (CD34(+), PAS(-)) could be seen in the transplantated tumors. Activated carbon particles were observed in all three types of vessels. CD31(+) cells adherent to the luminal surface of vessel wall. CD34(+) cells distributed along the vessels as well, but morphologically were more like a transition type between tumor cells and endothelial cells. Human specific Ki67 and HLA positive cells could be seen in the tumor vessels indicating that these vessels were derived from human tumor cells. Moreover, cells of tumor vessels were proved to be constructed by human tumor cells mainly and fusion cells of host cells and tumor cells under confocal microscope.

CONCLUSIONS

Three types of blood supply sources including endothelium-dependent vessels, vasculogenic mimicry (VMs) and mosaic vessels (MVs) exist in transplantation tumors of human glioma. Glioma stem and progenitor cells (GSCPs) have the potential to differentiate and transdifferentiate into VMs and MVs.

摘要

目的

在许多实体瘤中发现血管生成拟态(VM),这表明肿瘤细胞自身可参与肿瘤血管的构建。然而,这些细胞的起源仍未完全阐明,且这些血管是否具有供血能力也尚不清楚。开展初步研究以探究肿瘤新生血管的一部分是否源自肿瘤干细胞(TSCs)以及TSCs衍生的血管是否具有功能。

方法

将取自皮下和原位移植裸鼠模型的移植性胶质瘤组织制成石蜡切片。为鉴定肿瘤血管的细胞起源和类型,切片分别用CD31、CD34、CD133、GFAP、Ki67和HLA进行染色。同时进行CD34-PAS染色。部分荷瘤小鼠通过体循环灌注活性炭,观察活性炭的分布情况。

结果

CD34-PAS染色显示,在移植瘤中可观察到内皮依赖性血管(CD34(+),PAS(+))、VM血管(CD34(-),PAS(+))和镶嵌血管(MVs,CD34(+),PAS(-))。在所有这三种类型的血管中均观察到活性炭颗粒。CD31(+)细胞附着于血管壁腔面。CD34(+)细胞也沿血管分布,但形态上更像是肿瘤细胞与内皮细胞之间的过渡类型。在肿瘤血管中可见人特异性Ki67和HLA阳性细胞,表明这些血管源自人肿瘤细胞。此外,在共聚焦显微镜下证实肿瘤血管细胞主要由人肿瘤细胞以及宿主细胞与肿瘤细胞的融合细胞构成。

结论

人胶质瘤移植瘤中存在三种供血来源,包括内皮依赖性血管、血管生成拟态(VMs)和镶嵌血管(MVs)。胶质瘤干细胞和祖细胞(GSCPs)具有分化和转分化为VMs和MVs的潜能。

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