Yang Wei-Hsun, Cheng Chun-Yu, Chen Miao-Fen, Wang Ting-Chung
Division of Neurosurgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan, R.O.C.
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, R.O.C.
Anticancer Res. 2018 Sep;38(9):5183-5192. doi: 10.21873/anticanres.12841.
BACKGROUND/AIM: Glioma is the most common and lethal primary brain tumor. Even with the development of multidisciplinary treatment approaches, results are disappointing because of the unavoidable tumor recurrence, which may be caused by the existence of tumor-initiating cells. The p75 neurotrophin receptor (p75NTR), which belongs to the tumor necrosis factor receptor superfamily, is not only involved in various cellular functions but also related to tumor growth. This study is focused, on the possible role of p75NTR in glioma tumor initiation.
C6 cells with high and low expression of p75NTR were sorted using flow cytometry. The neurosphere characteristics and properties of these two subpopulations were assessed and compared with those of parental cells. Radiation and chemotherapy sensitivity was also analyzed in these cell populations. Finally, in vivo tumorigenicity of cells was tested in a rat model.
Cells overexpressing p75NTR (C6p75+++ cells) demonstrated greater ability of neurosphere formation, colony proliferation, and certain stem cell marker overexpression than cells with low p75NTR expression (C6p75+) and parental cells. In addition, following irradiation or temozolomide treatment, more viable C6p75+++ cells remained, and they proliferated into more colonies. In vivo, C6p75+++ cell implantation in Sprague Dawley rats reduced the survival time.
Cells with p75NTR overexpression demonstrated certain unique characteristics of tumor-initiating cells, such as neurosphere formation, high colony proliferation, and resistance to radio- and chemotherapy. With regard to the heterogeneous composition of glioma cells, p75NTR can be used as an alternative marker to identify a glioma subpopulation with tumor-initiating properties.
背景/目的：胶质瘤是最常见且致命的原发性脑肿瘤。即便多学科治疗方法有所发展，但由于不可避免的肿瘤复发，治疗结果仍令人失望，而肿瘤复发可能是由肿瘤起始细胞的存在所致。p75神经营养因子受体（p75NTR）属于肿瘤坏死因子受体超家族，不仅参与多种细胞功能，还与肿瘤生长相关。本研究聚焦于p75NTR在胶质瘤起始中的可能作用。
采用流式细胞术分选p75NTR高表达和低表达的C6细胞。评估并比较这两个亚群与亲代细胞的神经球特征和特性。还分析了这些细胞群体对放疗和化疗的敏感性。最后，在大鼠模型中测试细胞的体内致瘤性。
与低p75NTR表达细胞（C6p75 +）和亲代细胞相比，过表达p75NTR的细胞（C6p75 +++细胞）表现出更强的神经球形成能力、集落增殖能力以及某些干细胞标志物的过表达。此外，在接受照射或替莫唑胺治疗后，存活的C6p75 +++细胞更多，且它们增殖形成更多集落。在体内，将C6p75 +++细胞植入Sprague Dawley大鼠体内会缩短生存时间。
p75NTR过表达的细胞表现出某些肿瘤起始细胞的独特特征，如神经球形成、高集落增殖以及对放疗和化疗的抗性。鉴于胶质瘤细胞的异质性组成，p75NTR可作为一种替代标志物来识别具有肿瘤起始特性的胶质瘤亚群。
