Development of patient-derived xenograft models from a spontaneously immortal low-grade meningioma cell line, KCI-MENG1.
Development of patient-derived xenograft models from a spontaneously immortal low-grade meningioma cell line, KCI-MENG1.
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DOI：
10.1186/s12967-015-0596-8
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发表时间：
2015-07-15
影响因子：
7.4
通讯作者：
Mittal S
中科院分区：
文献类型：
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作者：
Michelhaugh SK;Guastella AR;Varadarajan K;Klinger NV;Parajuli P;Ahmad A;Sethi S;Aboukameel A;Kiousis S;Zitron IM;Ebrahim SA;Polin LA;Sarkar FH;Bollig-Fischer A;Mittal S
复发性/侵袭性脑膜瘤的有效治疗方法很少。建立改良的脑膜瘤体外和体内模型将有助于开发和测试新的治疗方法。一个原发性脑膜瘤细胞系是从一个嗅沟脑膜瘤患者产生的。通过生长动力学、免疫细胞化学、端粒酶活性、核型和比较基因组杂交分析对细胞系进行了广泛的表征。还开发了使用免疫受损的SCID小鼠的异种移植物模型。患者肿瘤的组织学与WHO I级典型脑膜瘤一致，由脑膜瘤细胞、螺旋和偶尔的沙瘤体组成。原始肿瘤和早期传代的原代细胞具有与低级别、预后良好的脑膜瘤一致的标准免疫组化特征。低代KCI-MENG 1细胞由梭形和圆形两种细胞类型组成，呈线性生长曲线，端粒酶活性极低，细胞遗传学分析显示由两个不同的无关克隆组成。相比之下，高传代细胞均匀圆形，生长迅速，具有高端粒酶活性，并且由具有近三倍体核型的单个克隆组成，所述近三倍体核型含有64-66条染色体，具有许多畸变。皮下和原位移植低传代细胞到SCID小鼠，波形蛋白和孕激素受体（PR）阳性的坚定的肿瘤形成，而皮下植入高传代细胞产生波形蛋白阳性，PR阴性的肿瘤，符合高级别脑膜瘤。虽然来源于良性脑膜瘤标本，但新建立的自发永生KCI-MENG 1脑膜瘤细胞系可用于生成具有低级别或高级别特征的异种移植肿瘤模型，这取决于细胞传代次数（可能是由于圆形近三倍体细胞的相对丰度）。这些人脑膜瘤小鼠异种移植模型将提供生物学相关平台，以研究低级别与高级别脑膜瘤肿瘤生物学和疾病进展的差异，以及开发新的疗法以改善预后不良或复发性脑膜瘤的治疗选择。本文的在线版本（doi：10.1186/s12967-015-0596-8）包含补充材料，可供授权用户使用。
There is a paucity of effective therapies for recurrent/aggressive meningiomas. Establishment of improved in vitro and in vivo meningioma models will facilitate development and testing of novel therapeutic approaches. A primary meningioma cell line was generated from a patient with an olfactory groove meningioma. The cell line was extensively characterized by performing analysis of growth kinetics, immunocytochemistry, telomerase activity, karyotype, and comparative genomic hybridization. Xenograft models using immunocompromised SCID mice were also developed. Histopathology of the patient tumor was consistent with a WHO grade I typical meningioma composed of meningothelial cells, whorls, and occasional psammoma bodies. The original tumor and the early passage primary cells shared the standard immunohistochemical profile consistent with low-grade, good prognosis meningioma. Low passage KCI-MENG1 cells were composed of two cell types with spindle and round morphologies, showed linear growth curve, had very low telomerase activity, and were composed of two distinct unrelated clones on cytogenetic analysis. In contrast, high passage cells were homogeneously round, rapidly growing, had high telomerase activity, and were composed of a single clone with a near triploid karyotype containing 64–66 chromosomes with numerous aberrations. Following subcutaneous and orthotopic transplantation of low passage cells into SCID mice, firm tumors positive for vimentin and progesterone receptor (PR) formed, while subcutaneous implant of high passage cells yielded vimentin-positive, PR-negative tumors, concordant with a high-grade meningioma. Although derived from a benign meningioma specimen, the newly-established spontaneously immortal KCI-MENG1 meningioma cell line can be utilized to generate xenograft tumor models with either low- or high-grade features, dependent on the cell passage number (likely due to the relative abundance of the round, near-triploid cells). These human meningioma mouse xenograft models will provide biologically relevant platforms from which to investigate differences in low- vs. high-grade meningioma tumor biology and disease progression as well as to develop novel therapies to improve treatment options for poor prognosis or recurrent meningiomas. The online version of this article (doi:10.1186/s12967-015-0596-8) contains supplementary material, which is available to authorized users.