The effects of type I interferon on glioblastoma cancer stem cells
The effects of type I interferon on glioblastoma cancer stem cells
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DOI：
10.1016/j.bbrc.2017.07.098
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发表时间：
2017-09-16
影响因子：
3.1
通讯作者：
Pfeffer, Lawrence M.
中科院分区：
文献类型：
--
作者：
Du, Ziyun;Cai, Chun;Pfeffer, Lawrence M.
胶质母细胞瘤(GBM)是一种高度侵袭性的脑肿瘤，极其致命。GBM的高度侵袭性及其在分子和细胞水平上的异质性被归因于罕见的GBM干细胞亚群(GSCs)。干扰素(IFN)是一类在体外具有抗癌活性的内源性抗病毒蛋白家族，已被临床用于治疗GBM。干扰素可抑制多种已建立的GBM细胞系的增殖，但IFN对GSCs的作用尚不清楚。本研究旨在探讨干扰素对免疫缺陷小鼠肾小球系膜细胞(GBM)异种移植的GSCs增殖和分化能力的影响。我们发现，干扰素抑制GSCs的增殖，抑制GSCs的球体形成能力，这是肿瘤干细胞的标志，并抑制GSCs分化为星形细胞的能力。此外，我们还发现，干扰素可诱导星形胶质细胞瞬时激活STAT3，而诱导星形胶质细胞分化可持续激活STAT3。(C)2017 Elsevier Inc.保留所有权利。
Glioblastomas (GBMs) are highly invasive brain tumors that are extremely deadly. The highly aggressive nature of GBM as well as its heterogeneity at the molecular and cellular levels has been attributed to a rare subpopulation of GBM stem-like cells (GSCs). Interferons (IFNs) are a family of endogenous antiviral proteins that have anticancer activity in vitro, and have been used clinically to treat GBM. IFN inhibits the proliferation of various established GBM cell lines, but the effects of IFNs on GSCs remain relatively unknown. The present study explored the effects of IFN on the proliferation and the differentiation capacity of GSCs isolated from GBM patient-derived xenolines (PDXs) grown as xenografts in immunocompromised mice. We show that IFN inhibits the proliferation of GSCs, inhibits the sphere forming capacity of GSCs that is a hallmark of cancer stem cells, and inhibits the ability of GSCs to differentiate into astrocytic cells. In addition, we show that IFN induces transient STAT3 activation in GSCs, while induction of astrocytic differentiation in GSCs results in sustained STAT3 activation. (C) 2017 Elsevier Inc. All rights reserved.