Kang Mi K, Hur Beong I, Ko Mi H, Kim Cheul H, Cha Seung H, Kang Soo K
Department of Physiology, College of Medicine, Pusan National University, Busan, Korea.
BMC Neurosci. 2008 Jan 30;9:15. doi: 10.1186/1471-2202-9-15.
Glioblastoma multiforme (GBM) is the most frequently encountered brain cancer. Although the existence of cancer stem cells in GBM has been previously established, there is little evidence to explain the difference between cancer stem cells and radio-resistant cells in GBM. In an effort to increase our understanding of whether cellular radio-resistance is a characteristic associated with cancer stem cells, we developed a dissociated cell system of subpopulations derived from GBM, and demonstrated radiotherapy resistance therein.
The radio-resistant cancer cell subpopulations of GBM abundantly express CD133, CD117, CD71, and CD45 surface markers, and these radio-resistant cancer cell subpopulations have the capacity for extensive proliferation, self-renewal, and pluripotency. These radio-resistant cancer subpopulations have been shown to initiate tumorigenesis when transplanted into SCID mouse brains. Moreover, these tumors evidenced highly peculiar nest-like shapes harboring both vascular and cancerous tissue structures, which expressed the blood vessel specific marker, the von Willebrand factor. Accordingly, subpopulations of radio-resistant cells in GBM have been shown to be very similar to hematopoietic stem cells (HSCs) in the circulating blood. This similarity may contribute to increased tumor growth and GBM recurrence.
The results of the present study provide further evidence for radio resistant subpopulations of cancer stem cells in GBM. Also, our results will assist in the identification and characterization of cancer stem cell populations in glioma, and will help to improve the therapeutic outcomes of GBM.
多形性胶质母细胞瘤（GBM）是最常见的脑癌。尽管此前已证实GBM中存在癌症干细胞，但几乎没有证据能解释GBM中癌症干细胞与放射抗性细胞之间的差异。为了增进我们对细胞放射抗性是否为癌症干细胞相关特征的理解，我们构建了一个源自GBM的亚群解离细胞系统，并在其中证实了放射抗性。
GBM的放射抗性癌细胞亚群大量表达CD133、CD117、CD71和CD45表面标志物，并且这些放射抗性癌细胞亚群具有广泛增殖、自我更新和多能性的能力。这些放射抗性癌症亚群已被证明在移植到SCID小鼠脑内时可引发肿瘤形成。此外，这些肿瘤呈现出高度独特的巢状形态，兼具血管和癌组织结构，表达血管特异性标志物血管性血友病因子。因此，GBM中放射抗性细胞亚群已被证明与循环血液中的造血干细胞（HSCs）非常相似。这种相似性可能导致肿瘤生长增加和GBM复发。
本研究结果为GBM中癌症干细胞的放射抗性亚群提供了进一步证据。此外，我们的结果将有助于识别和表征胶质瘤中的癌症干细胞群体，并有助于改善GBM的治疗效果。
