ROCK Inhibition Facilitates In Vitro Expansion of Glioblastoma Stem-Like Cells.
ROCK Inhibition Facilitates In Vitro Expansion of Glioblastoma Stem-Like Cells.
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DOI：
10.1371/journal.pone.0132823
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kim Y
中科院分区：
文献类型：
--
作者：
Tilson SG;Haley EM;Triantafillu UL;Dozier DA;Langford CP;Gillespie GY;Kim Y
由于其类似干细胞的特征以及对现有化疗和放疗的抵抗力，人们越来越认识到癌症干细胞（CSC）是癌症转移和复发的根本原因。然而，这些细胞代表癌细胞的一小部分，并且难以在体外繁殖。胶质母细胞瘤是一种极其致命的脑癌，推测其具有称为胶质母细胞瘤干细胞 (GSC；也称为脑肿瘤起始细胞，BTIC) 的 CSC 亚群。我们建议使用选择性 Rho 激酶 (ROCK) 抑制剂 Y-27632 和法舒地尔来促进 GSC/BTIC 样细胞在体外的存活和增殖。 ROCK 抑制剂与抑制细胞凋亡有关，并且假设它们会增加体外生长的 GSC/BTIC 样细胞的数量并提高克隆效率。事实上，我们的数据表明，瞬时和持续补充无毒浓度的 Y-27632 和法舒地尔可抑制细胞凋亡，增强细胞形成球体的能力，并增加表达 GSC/BTIC 样细胞亚群的干细胞标记物。我们的数据表明，ROCK 通路的药理学和遗传学 (siRNA) 抑制促进 GSC/BTIC 样细胞的体外扩增。因此，ROCK 通路抑制为未来 CSC 培养基的优化带来了希望。
Due to their stem-like characteristics and their resistance to existing chemo- and radiation therapies, there is a growing appreciation that cancer stem cells (CSCs) are the root cause behind cancer metastasis and recurrence. However, these cells represent a small subpopulation of cancer cells and are difficult to propagate in vitro. Glioblastoma is an extremely deadly form of brain cancer that is hypothesized to have a subpopulation of CSCs called glioblastoma stem cells (GSCs; also called brain tumor initiating cells, BTICs). We propose the use of selective Rho-kinase (ROCK) inhibitors, Y-27632 and fasudil, to promote GSC/BTIC-like cell survival and propagation in vitro. ROCK inhibitors have been implicated in suppressing apoptosis, and it was hypothesized that they would increase the number of GSC/BTIC-like cells grown in vitro and improve cloning efficiencies. Indeed, our data demonstrate that transient and continuous supplementation of non-toxic concentrations of Y-27632 and fasudil inhibited apoptosis, enhanced the cells’ ability to form spheres, and increased stem cell marker expressing GSC/BTIC-like cell subpopulation. Our data indicated that pharmacological and genetic (siRNA) inhibitions of the ROCK pathway facilitates in vitro expansion of GSC/BTIC-like cells. Thus, ROCK pathway inhibition shows promise for future optimization of CSC culture media.