Isolation of tumour stem-like cells from benign tumours.
Isolation of tumour stem-like cells from benign tumours.
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DOI：
10.1038/sj.bjc.6605142
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发表时间：
2009-07-21
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
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癌性干细胞样细胞（CSCs）被认为是一系列恶性肿瘤中的癌症起始细胞。不同的遗传程序调节CSC行为，胶质母细胞瘤患者的CSC在质量上彼此不同。CSC的存在和恶性肿瘤之间的内在联系尚不清楚。我们着手测试是否可以从良性肿瘤中识别出肿瘤干细胞样细胞。肿瘤球培养物来源于p53阳性和p53阴性垂体腺瘤。肿瘤干细胞样细胞在体外进行表征，使用自我更新试验，干细胞相关的标志物表达分析，分化，和刺激的激素产生测定。这些肿瘤干细胞样细胞的肿瘤起始能力在使用SCID小鼠的系列脑肿瘤移植实验中进行了测试。在这项研究中，我们从垂体腺瘤（一种良性肿瘤）中分离出球形、自我更新和多能干细胞样细胞。我们发现，垂体腺瘤干细胞样细胞（PASC），与他们的分化的子细胞相比，表达干细胞相关的基因产物，抗凋亡蛋白和垂体祖细胞标记物的水平增加。与从胶质母细胞瘤中分离的CSC类似，PASC比其分化的子细胞对化疗药物更具抗性。此外，分化的PASC对下丘脑激素的刺激作出反应，并产生相应的垂体激素，反映了原发性垂体肿瘤的表型。最后，我们在系列移植动物实验中证实PASCs是垂体肿瘤起始细胞。这项研究首次表明干细胞样细胞存在于良性肿瘤中。这项研究的结论可能有助于理解垂体瘤的生物学和治疗，以及对肿瘤起始细胞概念的影响。
Cancerous stem-like cells (CSCs) have been implicated as cancer-initiating cells in a range of malignant tumours. Diverse genetic programs regulate CSC behaviours, and CSCs from glioblastoma patients are qualitatively distinct from each other. The intrinsic connection between the presence of CSCs and malignancy is unclear. We set out to test whether tumour stem-like cells can be identified from benign tumours. Tumour sphere cultures were derived from hormone-positive and -negative pituitary adenomas. Characterisation of tumour stem-like cells in vitro was performed using self-renewal assays, stem cell-associated marker expression analysis, differentiation, and stimulated hormone production assays. The tumour-initiating capability of these tumour stem-like cells was tested in serial brain tumour transplantation experiments using SCID mice. In this study, we isolated sphere-forming, self-renewable, and multipotent stem-like cells from pituitary adenomas, which are benign tumours. We found that pituitary adenoma stem-like cells (PASCs), compared with their differentiated daughter cells, expressed increased levels of stem cell-associated gene products, antiapoptotic proteins, and pituitary progenitor cell markers. Similar to CSCs isolated from glioblastomas, PASCs are more resistant to chemotherapeutics than their differentiated daughter cells. Furthermore, differentiated PASCs responded to stimulation with hypothalamic hormones and produced corresponding pituitary hormones that are reflective of the phenotypes of the primary pituitary tumours. Finally, we demonstrated that PASCs are pituitary tumour-initiating cells in serial transplantation animal experiments. This study for the first time indicates that stem-like cells are present in benign tumours. The conclusions from this study may have applications to understanding pituitary tumour biology and therapies, as well as implications for the notion of tumour-initiating cells in general.
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