Department of Neurosurgery, Medical School Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
J Neurosci Methods. 2012 Mar 30;205(1):1-9. doi: 10.1016/j.jneumeth.2011.12.009. Epub 2011 Dec 23.
Although surgical resection of benign human meningiomas is the primary goal, in case of relapse or when they are not fully resectable, other strategies including chemotherapeutical treatment would be appropriate. The initial evaluation of chemotherapeutical agents requires an appropriate tumor model, where the natural characteristics of the original benign tumor is reflected. We here tested, whether primary cell cultures of benign human meningiomas would reliably grow after intracranial transplantation into mice, and whether they would show histomorphological and immunohistochemical characteristics of the original human tumor. Cells of 11 benign human meningiomas were transplanted into the prefrontal cortex of nude mice. After 3 months, the mice were sacrificed and their brains were histologically processed for morphological characterization and measurement of tumor volume. Additionally, the proliferation index (PI), the microvessel density, and epithelial membrane antigen (EMA) were compared between human meningiomas and tumors grown in mice by using immunohistochemical methods. Further, cyclooxygenase-2 (COX-2) expression, a possible target for pharmacological manipulation, was examined. The results showed in almost all mice (93%) a tumor formation with meningothelial histomorphology comparable to the original human tumors. The PI, vascular density and COX-2 expression were similar between human and mice meningiomas, but EMA expression was reduced in mice (P<0.01). In conclusion an implantation of benign human meningioma primary cell cultures in mice reliably results in tumor formation with morphological and immunohistological features comparable to the original human tumor. This model may therefore be suitable to test novel therapeutic agents.
虽然手术切除良性人脑膜瘤是主要目标,但在复发或无法完全切除时,其他策略,包括化疗,将是合适的。化疗药物的初步评估需要一个适当的肿瘤模型,反映原始良性肿瘤的自然特征。我们在这里测试了良性人脑膜瘤原代细胞培养物在颅内移植到小鼠后是否能可靠地生长,以及它们是否会表现出与原始人类肿瘤相同的组织形态学和免疫组织化学特征。将 11 例良性人脑膜瘤细胞移植到裸鼠的前额皮质。3 个月后,处死小鼠,对其大脑进行组织学处理,以进行形态学特征描述和肿瘤体积测量。此外,还通过免疫组织化学方法比较了人脑膜瘤与在小鼠中生长的肿瘤之间的增殖指数(PI)、微血管密度和上皮膜抗原(EMA)。进一步研究了环氧化酶-2(COX-2)的表达,这可能是药物干预的一个靶点。结果显示,几乎所有小鼠(93%)都形成了脑膜瘤形态的肿瘤,与原始人类肿瘤相似。PI、血管密度和 COX-2 的表达在人源和鼠源脑膜瘤之间相似,但 EMA 的表达在鼠源脑膜瘤中降低(P<0.01)。总之,将良性人脑膜瘤原代细胞培养物植入小鼠体内可可靠地形成具有与原始人类肿瘤相似的形态学和免疫组织化学特征的肿瘤。因此,该模型可能适用于测试新的治疗药物。