Du Ziyun, Cai Chun, Sims Michelle, Boop Frederick A, Davidoff Andrew M, Pfeffer Lawrence M
Department of Pathology and Laboratory Medicine, Center for Cancer Research, Memphis, TN, USA.
Department of Pathology and Laboratory Medicine, Center for Cancer Research, Memphis, TN, USA; Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, TN, USA.
Biochem Biophys Res Commun. 2017 Sep 16;491(2):343-348. doi: 10.1016/j.bbrc.2017.07.098. Epub 2017 Jul 18.
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.
胶质母细胞瘤（GBM）是极具侵袭性且极其致命的脑肿瘤。GBM的高度侵袭性及其在分子和细胞水平上的异质性归因于一种罕见的GBM干细胞样细胞（GSC）亚群。干扰素（IFN）是一类内源性抗病毒蛋白，在体外具有抗癌活性，并已在临床上用于治疗GBM。IFN可抑制多种已建立的GBM细胞系的增殖，但IFN对GSC的影响仍相对未知。本研究探讨了IFN对从在免疫缺陷小鼠中作为异种移植生长的GBM患者来源异种移植物（PDX）中分离出的GSC的增殖和分化能力的影响。我们发现IFN可抑制GSC的增殖，抑制作为癌症干细胞标志的GSC的成球能力，并抑制GSC分化为星形细胞的能力。此外，我们还发现IFN可在GSC中诱导STAT3短暂激活，而GSC中星形细胞分化的诱导则导致STAT3持续激活。
