Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
NMR Biomed. 2012 Apr;25(4):506-13. doi: 10.1002/nbm.1763. Epub 2011 Jul 27.
In the last decade, evidence has emerged indicating that the growth of a vast majority of tumors including gliomas is sustained by a subpopulation of cancer cells with stem cell properties called cancer initiating cells. These cells are able to initiate and propagate tumors and constitute only a fraction of all tumor cells. In the present study, we showed that intracerebral injection of cultured glioma-initiating cells into nude mice produced fast growing tumors showing necrosis and gadolinium enhancement in MR images, whereas gliomas produced by injecting freshly purified glioma-initiating cells grew slowly and showed no necrosis and very little gadolinium enhancement. Using proton localized spectroscopy at 14.1 Tesla, decreasing trends of N-acetylaspartate, glutamate and glucose concentrations and an increasing trend of glycine concentration were observed near the injection site after injecting cultured glioma-initiating cells. In contrast to the spectra of tumors grown from fresh cells, those from cultured cells showed intense peaks of lipids, increased absolute concentrations of glycine and choline-containing compounds, and decreased concentrations of glutamine, taurine and total creatine, when compared with a contralateral non-tumor-bearing brain tissue. A decrease in concentrations of N-acetylaspartate and γ-aminobutyrate was found in both tumor phenotypes after solid tumor formation. Further investigation is needed to determine the cause of the dissimilarities between the tumors grown from cultured glioma-initiating cells and those from freshly purified glioma-initiating cells, both derived from human glioblastomas.
在过去的十年中,有证据表明,包括神经胶质瘤在内的绝大多数肿瘤的生长是由具有干细胞特性的癌细胞亚群维持的,这些细胞被称为肿瘤起始细胞。这些细胞能够启动和增殖肿瘤,并且只占所有肿瘤细胞的一小部分。在本研究中,我们表明,将培养的神经胶质瘤起始细胞脑内注射到裸鼠体内会产生快速生长的肿瘤,在磁共振图像上显示出坏死和钆增强,而注射新鲜纯化的神经胶质瘤起始细胞产生的肿瘤生长缓慢,没有坏死,很少有钆增强。在 14.1T 质子定位光谱中,在注射培养的神经胶质瘤起始细胞后,在注射部位附近观察到 N-乙酰天冬氨酸、谷氨酸和葡萄糖浓度的下降趋势,以及甘氨酸浓度的上升趋势。与来自新鲜细胞的肿瘤光谱相比,来自培养细胞的肿瘤光谱显示出强烈的脂质峰、甘氨酸和含胆碱化合物的绝对浓度增加,以及谷氨酰胺、牛磺酸和总肌酸的浓度降低,与对侧非肿瘤性脑组织相比。在固体肿瘤形成后,两种肿瘤表型中的 N-乙酰天冬氨酸和γ-氨基丁酸浓度都降低了。需要进一步研究以确定源自人神经胶质瘤的培养的神经胶质瘤起始细胞和新鲜纯化的神经胶质瘤起始细胞产生的肿瘤之间的差异的原因。