A novel, diffusely infiltrative xenograft model of human anaplastic oligodendroglioma with mutations in FUBP1, CIC, and IDH1.
A novel, diffusely infiltrative xenograft model of human anaplastic oligodendroglioma with mutations in FUBP1, CIC, and IDH1.
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DOI：
10.1371/journal.pone.0059773
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Nigro JM
中科院分区：
文献类型：
--
作者：
Klink B;Miletic H;Stieber D;Huszthy PC;Campos Valenzuela JA;Balss J;Wang J;Schubert M;Sakariassen PØ;Sundstrøm T;Torsvik A;Aarhus M;Mahesparan R;von Deimling A;Kaderali L;Niclou SP;Schröck E;Bjerkvig R;Nigro JM
少突胶质细胞瘤对恶性成人胶质瘤构成生物学难题：它是一种普遍无法治愈的肿瘤类型，然而，只有少数人类肿瘤已被建立为体外细胞群或体内颅内异种移植物。因此，它们的生存只能在特定的环境背景下出现。为了确定人少突胶质细胞瘤在实验模型中的命运，我们研究了颅内植入增强型绿色荧光蛋白（eGFP）阳性NOD/SCID小鼠后间变性肿瘤的发展。值得注意的是，近9个月后，肿瘤不仅移植，而且还保留了人类少突胶质细胞瘤的经典组织学和遗传学特征，特别是具有透明细胞质的细胞，显示出浸润性生长模式，并携带IDH 1（R132 H）和肿瘤抑制基因FUBP 1和CIC的突变。异种移植物具有高度侵袭性，在神经元周围表现出明显的迁移和生长模式，特别是在海马中，并且在胼胝体的白色物质束之后，肿瘤细胞在已建立的血管系统周围积聚。尽管肿瘤在体内表现出高生长分数，但在六个月的时间内，来自原始患者肿瘤的细胞和异种移植物都没有表现出显著的体外生长。该胶质瘤异种移植物是第一个显示出纯少突胶质细胞瘤组织学和R132 H表达的。出乎意料的属性，即细胞未能在体外生长，即使通过小鼠后，使我们能够独特地调查这种少突胶质细胞瘤与体内微环境的关系。
Oligodendroglioma poses a biological conundrum for malignant adult human gliomas: it is a tumor type that is universally incurable for patients, and yet, only a few of the human tumors have been established as cell populations in vitro or as intracranial xenografts in vivo. Their survival, thus, may emerge only within a specific environmental context. To determine the fate of human oligodendroglioma in an experimental model, we studied the development of an anaplastic tumor after intracranial implantation into enhanced green fluorescent protein (eGFP) positive NOD/SCID mice. Remarkably after nearly nine months, the tumor not only engrafted, but it also retained classic histological and genetic features of human oligodendroglioma, in particular cells with a clear cytoplasm, showing an infiltrative growth pattern, and harboring mutations of IDH1 (R132H) and of the tumor suppressor genes, FUBP1 and CIC. The xenografts were highly invasive, exhibiting a distinct migration and growth pattern around neurons, especially in the hippocampus, and following white matter tracts of the corpus callosum with tumor cells accumulating around established vasculature. Although tumors exhibited a high growth fraction in vivo, neither cells from the original patient tumor nor the xenograft exhibited significant growth in vitro over a six-month period. This glioma xenograft is the first to display a pure oligodendroglioma histology and expression of R132H. The unexpected property, that the cells fail to grow in vitro even after passage through the mouse, allows us to uniquely investigate the relationship of this oligodendroglioma with the in vivo microenvironment.
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影响因子：
12.7
作者：
Hartmann, Christian;Meyer, Jochen;von Deimling, Andreas
通讯作者：
von Deimling, Andreas
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Lu, Chao;Ward, Patrick S.;Kapoor, Gurpreet S.;Rohle, Dan;Turcan, Sevin;Abdel-Wahab, Omar;Edwards, Christopher R.;Khanin, Raya;Figueroa, Maria E.;Melnick, Ari;Wellen, Kathryn E.;O'Rourke, Donald M.;Berger, Shelley L.;Chan, Timothy A.;Levine, Ross L.;Mellinghoff, Ingo K.;Thompson, Craig B.
通讯作者：
Thompson, Craig B.
影响因子：
10.5
作者：
Dai, C;Celestino, JC;Holland, EC
通讯作者：
Holland, EC
影响因子：
12.7
作者：
Capper, David;Zentgraf, Hanswalter;von Deimling, Andreas
通讯作者：
von Deimling, Andreas