Standardization of an orthotopic mouse brain tumor model following transplantation of CT-2A astrocytoma cells
Standardization of an orthotopic mouse brain tumor model following transplantation of CT-2A astrocytoma cells
复制标题
DOI：
10.14670/hh-22.1309
复制
发表时间：
2007-12-01
影响因子：
2
通讯作者：
Martinez, A.
中科院分区：
文献类型：
--
作者：
Martinez-Murillo, R.;Martinez, A.
胶质源性肿瘤的动物模型是研究胶质瘤肿瘤发生的生物学机制和维持疾病状态的生物学机制所必需的。为了开发和表征浸润性星形细胞瘤的合适的体内实验小鼠模型，具有重现人星形细胞瘤的可预测和可重现的生长模式，本研究分析了C57 BL/6 J小鼠中同基因原位植入CT-2A小鼠星形细胞瘤的长期病程。颅内注射CT-2A细胞到尾壳核导致发展的侵略性肿瘤显示人类多形性胶质母细胞瘤的典型特征，共享密切的组织学，免疫组化，增殖和代谢概况。为了模拟脑转移性疾病，通过颈内动脉注射CT-2A细胞。获得与通过颅内注射获得的肿瘤相同的肿瘤。最后，从实验性脑肿瘤中重新分离CT-2A细胞，并经颅重新注射到健康小鼠的尾壳核中。这些细胞产生的新肿瘤与最初的肿瘤无法区分，表明肿瘤细胞在体内自我更新。小动物模型对于测试针对相关分子靶点的新型生物疗法至关重要。在一项初步研究中，实验CT-2A肿瘤用小分子77427长期治疗，这是一种抑制血管生成的胃泌素释放肽（GRP）阻断剂化合物。给药动物的肿瘤明显小于对照组，表明77427在胶质母细胞瘤中具有抗肿瘤作用。我们的结论是，原位CT-2A肿瘤模型，如本文所述，是适当的，以探索神经胶质瘤的发展机制和有前途的药物的临床前试验。
Animal models of glial-derived neoplasms are needed to study the biological mechanisms of glioma tumorigenesis and those that sustain the disease state. With the aim to develop and characterize a suitable in vivo experimental mouse model for infiltrating astrocytoma, with predictable and reproducible growth patterns that recapitulate human astrocytoma, this study was undertaken to analyze the long-term course of a syngeneic orthotopically implanted CT-2A mouse astrocytoma in C57BL/6J mice. Intracranial injection of CT-2A cells into caudate-putamen resulted in development of an aggressive tumor showing typical features of human glioblastoma multiforme, sharing close histological, immunohistochemical, proliferative, and metabolic profiles. To simulate metastatic disease to the brain, CT-2A cells were injected through the internal carotid artery. Tumors identical to those obtained by intracranial injection were obtained. Finally, CT-2A cells were re-isolated from experimental brain tumors and transcranially re-injected into the caudate-putamen of healthy mice. These cells generated new tumors that were indistinguishable from the initial ones, suggesting in vivo self-renewal of tumor cells. Small-animal models are essential for testing novel biological therapies directed against relevant molecular targets. In a preliminary study, experimental CT-2A tumors were chronically treated with the small molecule 77427, a gastrin-releasing peptide (GRP) blocker compound that inhibits angiogenesis. Treated animals developed significantly smaller tumors than controls, suggesting an antitumor action for 77427 in glioblastomas. We conclude that the orthotopic CT-2A tumor model, as described herein, is appropriate to explore the mechanisms of glioma development and for preclinical trials of promising drugs.