Blazek Ed R, Foutch Jennifer L, Maki Guitta
Radiation Oncology Department, Division of Hematology/Oncology, Rush University Medical Center, Chicago, IL 60612, USA.
Int J Radiat Oncol Biol Phys. 2007 Jan 1;67(1):1-5. doi: 10.1016/j.ijrobp.2006.09.037. Epub 2006 Nov 2.
Primary medulloblastoma and glioblastoma multiforme tumor cells that express the surface marker CD133 are believed to be enriched for brain tumor stem cells because of their unique ability to initiate or reconstitute tumors in immunodeficient mice. This study sought to characterize the radiobiological properties and marker expression changes of CD133+ vs. CD133- cells of an established medulloblastoma cell line.
Daoy and D283 Med cell lines were stained with fluorescently labeled anti-CD133 antibody and sorted into CD133+ and CD133- populations. The effect of oxygen (2% vs. 20%) on CD133 expression was measured. Both populations were analyzed for marker stability, cell cycle distribution, and radiosensitivity.
CD133+ Daoy cells restored nearly native CD133+ and CD133- populations within 18 days, whereas CD133- cells remained overwhelmingly CD133-. Culturing Daoy cells in 2% oxygen rather than the standard 20% oxygen increased their CD133 expression 1.6-fold. CD133+ Daoy cells were radioresistant via the beta-parameter of the linear-quadratic model relative to CD133- Daoy cells, although their alpha-parameters and cell cycle distributions were identical.
Restoration of the original CD133+ and CD133- populations from CD133+ Daoy cells in serum is further evidence that CD133+ cells are functionally distinct from CD133- cells. The radioresistance of CD133+ compared with CD133- Daoy cells is consistent with better repair of sublethal damage. Enlargement of the CD133+ sector is a new feature of the hypoxic response.
原发性髓母细胞瘤和多形性胶质母细胞瘤肿瘤细胞表达表面标志物CD133，因其具有在免疫缺陷小鼠体内启动或重建肿瘤的独特能力，被认为富含脑肿瘤干细胞。本研究旨在表征已建立的髓母细胞瘤细胞系中CD133 +与CD133 -细胞的放射生物学特性和标志物表达变化。
用荧光标记的抗CD133抗体对Daoy和D283 Med细胞系进行染色，并分选成CD133 +和CD133 -群体。测量氧气（2%与20%）对CD133表达的影响。分析两个群体的标志物稳定性、细胞周期分布和放射敏感性。
CD133 + Daoy细胞在18天内恢复了几乎天然的CD133 +和CD133 -群体，而CD133 -细胞绝大多数仍为CD133 -。将Daoy细胞在2%氧气而非标准的20%氧气中培养，其CD133表达增加了1.6倍。相对于CD133 - Daoy细胞，CD133 + Daoy细胞通过线性二次模型的β参数具有放射抗性，尽管它们的α参数和细胞周期分布相同。
血清中CD133 + Daoy细胞恢复原始的CD133 +和CD133 -群体，进一步证明CD133 +细胞在功能上与CD133 -细胞不同。与CD133 - Daoy细胞相比，CD133 +细胞的放射抗性与亚致死损伤的更好修复一致。CD133 +部分的扩大是缺氧反应的一个新特征。
