Glioblastoma formation from cell population depleted of Prominin1-expressing cells.

Glioblastoma formation from cell population depleted of Prominin1-expressing cells.
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DOI:
10.1371/journal.pone.0006869
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发表时间:
2009-08-31
期刊:
影响因子:
3.7
通讯作者:
Kondo T
Kondo T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Nishide K;Nakatani Y;Kiyonari H;Kondo T

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pronin1 (Prom1,在人类中也被称为CD133)已被广泛用作癌症干细胞(CSCs)的标记物,CSCs在包括多形胶质母细胞瘤(GBM)在内的恶性肿瘤中具有自我更新和致瘤性。然而,也有其他证据表明prom1阴性的癌细胞在体内也会形成肿瘤。因此,Prom1是否是CSCs的真正标记物仍然存在争议。为了验证表达Prom1的细胞是否是肿瘤发生所必需的,我们建立了一个小鼠系,其表达Prom1的细胞可以通过Prom1位点上的crec诱导的DTA基因和他莫昔芬诱导的CreERTM有条件地消除,并通过在小鼠系的神经干细胞中过表达SV40大T抗原和致癌的H-RasL61产生胶质瘤启动细胞(gscs - ld)。我们在这里展示了他莫昔芬处理的GICs-LD (GICs-DTA)在培养和体内可移植GBM中形成肿瘤球。因此,我们的研究表明,在这种小鼠模型中,表达prom1的细胞对于胶质瘤的形成是必不可少的。
Prominin1 (Prom1, also known as CD133 in human) has been widely used as a marker for cancer stem cells (CSCs), which self-renew and are tumorigenic, in malignant tumors including glioblastoma multiforme (GBM). However, there is other evidence showing that Prom1-negative cancer cells also form tumors in vivo. Thus it remains controversial whether Prom1 is a bona fide marker for CSCs. To verify if Prom1-expressing cells are essential for tumorigenesis, we established a mouse line, whose Prom1-expressing cells can be eliminated conditionally by a Cre-inducible DTA gene on the Prom1 locus together with a tamoxifen-inducible CreERTM, and generated glioma-initiating cells (GICs-LD) by overexpressing both the SV40 Large T antigen and an oncogenic H-RasL61 in neural stem cells of the mouse line. We show here that the tamoxifen-treated GICs-LD (GICs-DTA) form tumor-spheres in culture and transplantable GBM in vivo. Thus, our studies demonstrate that Prom1-expressing cells are dispensable for gliomagenesis in this mouse model.
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