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首页> 外文期刊>International journal of oncology >Increased in vivo angiogenic effect of glioma stromal mesenchymal stem-like cells on glioma cancer stem cells from patients with glioblastoma
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Increased in vivo angiogenic effect of glioma stromal mesenchymal stem-like cells on glioma cancer stem cells from patients with glioblastoma

机译:胶质瘤基质间充质干样细胞对胶质母细胞瘤患者胶质瘤癌干细胞的体内血管生成作用增强

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The presence of glioma stromal mesenchymal stem?like cells (GS-MSLCs) in tumors from glioma patients has been previously reported. The mechanisms through which these cells function as a part of the glioma microenvironment, however, remain incompletely understood. We investigated the biological effects of GS-MSLCs on glioma cancer stem cells (gCSCs), testing the hypothesis that GS-MSLCs alter the biological characteristics of gCSCs. GS-MSLCs and gCSCs were isolated from different glioblastoma (GBM) specimens obtained from patients. In in?vitro experiments, gCSCs were cultured alone or co-cultured with GS-MSLCs, and gCSCs cell counts were compared between the two groups. In addition, two groups of orthotopic GBM xenografts in mice were created, one using gCSCs from the monoculture group and one using gCSCs isolated from the co-culture group, and tumor volume and survival were analyzed. Furthermore, in?vivo proliferation, apoptosis and vessel formation were examined using immunohistochemical analyses. In?vitro cell counts for gCSCs co-cultured with GS-MSLCs increased 3-fold compared to gCSCs cultured alone. In orthotopic xenograft experiments, mice injected with gCSCs isolated from the co-culture group had significantly larger tumor volume, measured on day?40 after injection, and their survival times were shorter. Immunohistochemical analysis showed increased tumor expression of CD31, indicative of enhanced microvessel formation in mice injected with gCSCs co-cultured with GS-MSLCs compared to mice injected with gCSCs cultured alone. However, proliferation (PCNA) and apoptosis (TUNEL) markers showed no significant difference between the two groups. In conclusion, GS-MSLCs may influence the biological properties of gCSCs, shifting them towards a more aggressive status; moreover, increased angiogenesis may be a critical component of this mechanism.
机译:先前已经报道了来自神经胶质瘤患者的肿瘤中存在神经胶质瘤基质间充质干样细胞(GS-MSLC)。这些细胞作为神经胶质瘤微环境的一部分的机制尚不完全清楚。我们调查了GS-MSLC对神经胶质瘤癌干细胞(gCSCs)的生物学效应,检验了GS-MSLC改变gCSCs生物学特性的假设。 GS-MSLCs和gCSCs从获自患者的不同胶质母细胞瘤(GBM)标本中分离出来。在体外实验中,将gCSCs单独培养或与GS-MSLC共培养,然后比较两组之间的gCSCs细胞计数。另外,创建了两组小鼠原位GBM异种移植物,一组使用来自单培养组的gCSC,另一组使用从共培养组分离的gCSC,并分析了肿瘤体积和存活率。此外,使用免疫组织化学分析检查了体内增殖,凋亡和血管形成。与单独培养的gCSC相比,与GS-MSLC共培养的gCSC的体外细胞计数增加了3倍。在原位异种移植实验中,注射从共培养组分离的gCSC的小鼠在注射后第40天测得的肿瘤体积明显更大,并且它们的存活时间更短。免疫组织化学分析显示,与单独注射gCSC的小鼠相比,注射GS-MSLC的gCSC的小鼠中CD31的肿瘤表达增加,表明微血管形成增强。但是,增殖(PCNA)和凋亡(TUNEL)标记在两组之间没有显着差异。总之,GS-MSLCs可能会影响gCSCs的生物学特性,从而将其转变为更具侵略性的状态。此外,增加的血管生成可能是该机制的关键组成部分。

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