Antiangiogenic activity of BAI1 in vivo:: implications for gene therapy of human glioblastomas
Antiangiogenic activity of BAI1 in vivo:: implications for gene therapy of human glioblastomas
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DOI：
10.1038/sj.cgt.7700898
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发表时间：
2006-04-01
影响因子：
6.4
通讯作者：
Tani, K
中科院分区：
文献类型：
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作者：
Kang, X;Xiao, X;Tani, K
胶质母细胞瘤是成人中最常见的原发性脑肿瘤。这些肿瘤表现出高度的血管化，从星形细胞瘤到胶质母细胞瘤的恶性进展通常伴随着血管生成增加和血管内皮生长因子及其受体的上调。在这项研究中，我们研究了脑特异性血管生成抑制剂1（BAI1）使用人胶质母细胞瘤细胞系的体内抗血管生成和抗肿瘤作用。用编码BAI 1的腺病毒载体（AdBAI 1）转导胶质母细胞瘤细胞，北方和Western印迹分析分别证明BAI 1 mRNA和蛋白在转导的肿瘤细胞中表达。使用体内新血管生成试验，我们发现，周围的血管生成AdBAI1转导的胶质母细胞瘤细胞移植到透明的皮肤褶皱室的SCID小鼠相比，对照治疗的细胞显着受损。此外，在体内接种AdBAI 1建立皮下或脑内移植肿瘤显着损害肿瘤的生长，并促进增加小鼠生存。在形态学上，肿瘤表现出血管生成受损的迹象，如广泛坏死和肿瘤内血管密度降低。综上所述，这些数据强烈表明，BAI 1可能是一个很好的基因治疗候选人治疗脑肿瘤，特别是人类胶质母细胞瘤。
Glioblastomas are the most common primary brain tumors in adults. These tumors exhibit a high degree of vascularization, and malignant progression from astrocytoma to glioblastoma is often accompanied by increased angiogenesis and the upregulation of vascular endothelial growth factor and its receptors. In this study, we investigated the in vivo antiangiogenic and antitumor effects of brain-specific angiogenesis inhibitor 1 (BAI1) using human glioblastoma cell lines. Glioblastoma cells were transduced with an adenoviral vector encoding BAI1 (AdBAI1), and Northern and Western blot analyses, respectively, demonstrated BAI1 mRNA and protein expression in the transduced tumor cells. Using an in vivo neovascularization assay, we found that angiogenesis surrounding AdBAI1-transduced glioblastoma cells transplanted into transparent skinfold chambers of SCID mice was significantly impaired compared to control treated cells. Additionally, in vivo inoculation with AdBAI1 of established subcutaneous or intracerebral transplanted tumors significantly impaired tumor growth and promoted increased mouse survival. Morphologically, the tumors exhibited signs of impaired angiogenesis, such as extensive necrosis and reduced intratumoral vascular density. Taken together, these data strongly indicate that BAI1 may be an excellent gene therapy candidate for the treatment of brain tumors, especially human glioblastomas.