Glioma initiating cells contribute to malignant transformation of host glial cells during tumor tissue remodeling via PDGF signaling
Glioma initiating cells contribute to malignant transformation of host glial cells during tumor tissue remodeling via PDGF signaling
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胶质瘤起始细胞通过PDGF信号传导在肿瘤组织重塑过程中促进宿主胶质细胞的恶性转化
DOI：
10.1016/j.canlet.2015.05.026
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发表时间：
2015-09-01
期刊：
影响因子：
9.7
通讯作者：
Dong, Jun
中科院分区：
文献类型：
--
作者：
Chen, Yanming;Wang, Zhongyong;Dong, Jun
前言：胶质瘤起始细胞(GICs)在肿瘤的发生发展中起着重要作用。然而，肿瘤细胞与局部肿瘤微环境的宿主细胞之间的相互作用在很大程度上是未知的。除了GICs及其后代细胞外，在胶质瘤组织重塑过程中，邻近的正常胶质细胞是否参与了肿瘤的发生，值得进一步研究。方法：将红色荧光蛋白(RFP)基因稳定地导入人GIC细胞株SU3和U87中，然后将其移植到表达绿色荧光蛋白(GFP)的裸鼠脑内。在hGICs启动的组织重塑过程中，观察了GICs与宿主细胞在体内的相互作用。结果：在SU3诱导的双荧光异种胶质瘤模型中，部分克隆自脑内肿瘤的宿主细胞获得了无限增殖的能力。PCR和FISH结果表明恶性转化细胞来源于宿主细胞；细胞表面标志物分析表明这些细胞表达小鼠少突胶质细胞特异性标志物CNP和少突胶质细胞前体细胞(OPC)特异性标志物PDGFR-α和NG2。染色体分析表明，这些细胞是超四倍体。体内研究表明，它们具有高侵袭活性和近100%的致瘤率。与PDGF-B高表达的SU3细胞相比，低表达PDGF-B的U87细胞来源的GICs不能诱导宿主细胞转化。结论：原代高侵袭性GICs SU3可能通过PDGF/PDGFR信号激活促进邻近正常宿主神经胶质细胞在局部肿瘤微环境中的转化，值得进一步研究。(C)2015爱思唯尔爱尔兰有限公司。保留所有权利。
Introduction: Glioma initiating cells (GICs) play important roles in tumor initiation and progression. However, interactions between tumor cells and host cells of local tumor microenvironment are kept largely unknown. Besides GICs and their progeny cells, whether adjacent normal glial cells contribute to tumorigenesis during glioma tissue remodeling deserves further investigation.Methods: Red fluorescence protein (RFP) gene was stably transfected into human GIC cells lines SU3 and U87, then were transplanted intracerebrally into athymic nude mice with whole-body green fluorescence protein (GFP) expression. The interactions between GICs and host cells in vivo were observed during tissue remodeling processes initiated by hGICs. The biological characteristics of host glial cells with high proliferation capability cloned from the xenograft were further assayed.Results: In a SU3 initiated dual-fluorescence xenograft glioma model, part of host cells cloned from the intracerebral tumors were found acquiring the capability of unlimited proliferation. PCR and FISH results indicated that malignant transformed cells were derived from host cells; cell surface marker analysis showed these cells expressed murine oligodendrocyte specific marker CNP, and oligodendrocyte progenitor cells (OPCs) specific markers PDGFR-alpha and NG2. Chromosomal analysis showed these cells were super tetraploid. In vivo studies showed they behaved with high invasiveness activity and nearly 100% tumorigenic ratio. Compared with SU3 cells with higher PDGF-B expression, GICs derived from U87 cells with low level of PDGF-B expression failed to induce host cell transformation.Conclusions: Primary high invasive GICs SU3 contribute to transformation of adjacent normal host glial cells in local tumor microenvironment possibly via PDGF/PDGFR signaling activation, which deserved further investigation. (C) 2015 Elsevier Ireland Ltd. All rights reserved.