Clinical Neurosciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
Cancer Lett. 2012 Dec 29;326(1):79-87. doi: 10.1016/j.canlet.2012.07.022. Epub 2012 Jul 24.
It has been proposed that gliomas contain a subpopulation of 'Brain Tumor Stem Cells' (BTSCs), which demonstrate resistance to conventional therapies. A potential component of the environment governing the behavior of these BTSCs is a class of transmembrane proteins with structural and signaling functions, the A-Disintegrin And Metalloproteases (ADAMs). In this study we confirm overexpression of ADAM10 and 17 in human glioma tissue compared to human controls, and especially in tumor sphere cultures thought to enrich for BTSCs. Inhibition of ADAM10/17 function impairs the growth of tumor spheres with evidence of depletion of the sphere forming cell population. This results from a combination of reduced proliferation, cell death and a switch of sphere-forming cells away from symmetric self-renewal division towards neuronal differentiation. A developing appreciation of the role of ADAMs in BTSC promises insights into pathophysiology and potential therapeutic avenues in this intractable group of tumors.
已经有人提出，神经胶质瘤中存在一小部分“脑肿瘤干细胞”（BTSC），它们对常规治疗具有抗药性。这些 BTSC 行为的一个潜在环境组成部分是一类具有结构和信号功能的跨膜蛋白，即 A-解整合素和金属蛋白酶（ADAMs）。在这项研究中，我们证实与正常人脑组织相比，ADAM10 和 17 在人神经胶质瘤组织中过度表达，尤其是在肿瘤球体培养物中，这些培养物被认为富含 BTSC。ADAM10/17 功能的抑制会损害肿瘤球体的生长，并且有证据表明球体形成细胞群体减少。这是由于增殖减少、细胞死亡以及球体形成细胞从对称的自我更新分裂向神经元分化的转变的综合作用。ADAMs 在 BTSC 中的作用的不断发展的认识有望深入了解这组难以治疗的肿瘤的病理生理学和潜在治疗途径。
