Cell migration in paediatric glioma; characterisation and potential therapeutic targeting.
Cell migration in paediatric glioma; characterisation and potential therapeutic targeting.
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DOI：
10.1038/bjc.2015.16
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发表时间：
2015-02-17
影响因子：
8.8
通讯作者：
Bruening-Richardson, A.
中科院分区：
文献类型：
--
作者：
Cockle, J. V.;Picton, S.;Levesley, J.;Ilett, E.;Carcaboso, A. M.;Short, S.;Steel, L. P.;Melcher, A.;Lawler, S. E.;Bruening-Richardson, A.
小儿高级别胶质瘤（pHGG）和弥漫性内在脑桥胶质瘤（DIPG）是高度侵袭性的脑肿瘤。它们的侵袭性表型导致其有限的治疗反应，并且需要阻断脑肿瘤侵袭的新治疗。在这里，我们研究了小分子糖原合成酶激酶-3抑制剂氯化锂（LiCl）和靛玉红衍生物6-溴靛玉红肟（BIO）对两种pHGG细胞系的迁移特性和治疗效果，这些抑制剂先前显示出抑制成体神经胶质瘤细胞的迁移（SF 188和KNS 42）和一条患者源性DIPG线（HSJD-DIPG-007）使用2D（transwell膜，免疫荧光，活细胞成像）和3D（纳米纤维板上的迁移和胶原蛋白中的球状体侵入）测定。所有品系均为迁移性品系，但在形态和迁移率上存在差异。通过免疫荧光观察，氯化锂和BIO均减少了迁移，并引发了应力纤维和局灶性粘连的细胞骨架重排。在药物存在下，通过活细胞成像观察到极性丧失和细胞运动差异。我们是第一个研究表明，它是可能的，在体外使用氯化锂和BIO的儿科胶质瘤的靶向迁移，我们的结论是，这些代理及其衍生物值得进一步的临床前研究作为潜在的抗迁移治疗这些毁灭性的肿瘤。
Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are highly aggressive brain tumours. Their invasive phenotype contributes to their limited therapeutic response, and novel treatments that block brain tumour invasion are needed. Here, we examine the migratory characteristics and treatment effect of small molecule glycogen synthase kinase-3 inhibitors, lithium chloride (LiCl) and the indirubin derivative 6-bromoindirubin-oxime (BIO), previously shown to inhibit the migration of adult glioma cells, on two pHGG cell lines (SF188 and KNS42) and one patient-derived DIPG line (HSJD-DIPG-007) using 2D (transwell membrane, immunofluorescence, live cell imaging) and 3D (migration on nanofibre plates and spheroid invasion in collagen) assays. All lines were migratory, but there were differences in morphology and migration rates. Both LiCl and BIO reduced migration and instigated cytoskeletal rearrangement of stress fibres and focal adhesions when viewed by immunofluorescence. In the presence of drugs, loss of polarity and differences in cellular movement were observed by live cell imaging. Ours is the first study to demonstrate that it is possible to pharmacologically target migration of paediatric glioma in vitro using LiCl and BIO, and we conclude that these agents and their derivatives warrant further preclinical investigation as potential anti-migratory therapeutics for these devastating tumours.
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DOI：
10.1083/jcb.200802081
发表时间：
2008-06-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fackler OT;Grosse R
通讯作者：
Grosse R
DOI：
10.1016/j.jconrel.2012.04.045
发表时间：
2012-12-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Mehta G;Hsiao AY;Ingram M;Luker GD;Takayama S
通讯作者：
Takayama S
DOI：
10.1016/s1357-2725(02)00071-7
发表时间：
2003-01-01
影响因子：
4
作者：
Wehrle-Haller, B;Imhof, BA
通讯作者：
Imhof, BA
影响因子：
21.3
作者：
Hoessel, R;Leclerc, S;Meijer, L
通讯作者：
Meijer, L
影响因子：
5.1
作者：
van Beusechem, VW;Mastenbroek, DCJ;Gerritsen, WR
通讯作者：
Gerritsen, WR