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裸鼠人颅咽管瘤异种移植瘤中的血管生成与细胞增殖

Angiogenesis and cell proliferation in human craniopharyngioma xenografts in nude mice.

作者信息

Xu Jianguo, You Chao, Zhang Sizhong, Huang Siqing, Cai Bowen, Wu Zhenggui, Li Hao

机构信息

Department of Neurosurgery, West China Hospital, Sichuan University, People's Republic of China.

出版信息

J Neurosurg. 2006 Oct;105(4 Suppl):306-10. doi: 10.3171/ped.2006.105.4.306.

DOI:10.3171/ped.2006.105.4.306
PMID:17328281
Abstract

OBJECT

Craniopharyngioma is one of the most common congenital tumors of the sellar and suprasellar regions and accounts for between 4 and 6% of all intracranial tumors. Its oncogenesis and biological behavior have not been well studied, and neither a cell line nor an animal model have been established. To better understand the tumor and improve its clinical management, the authors investigated the angiogenesis and cellular proliferation in subcutaneous craniopharyngioma xenografts obtained by implanting human tumor cells into athymic nude mice.

METHODS

Human craniopharyngioma cells obtained from surgical specimens were subcutaneously implanted into BALB/c-nu/nu nude mice to establish a preliminary animal model of a transplanted tumor. Immunohistochemical staining with streptavidin-peroxidase complex was used to identify the cell phenotype and to evaluate the angiogenesis and proliferation in the xenografts. Expression of cytokeratin, minichromosome maintenance deficient 6 (MCM6) protein, and endothelial cell marker CD34 on the xenograft sections were assayed quantitatively by computer-assisted microscopy. Twenty-seven surviving subcutaneous xenografts were obtained in 15 nude mice. The total implantation success rate was 28.12% (adamantine epithelioma [AE], 37.50%; squamous papillary tumor [SPT], 18.75%). Formation of capillaries and cell proliferation were observed in all of these xenografts. Microvessel density and degree of MCM6 immunostaining were positively correlated in the surviving grafts (r = 0.410, p < 0.05), but there was no significant difference in these variables between the AE and SPT groups (p > 0.05).

CONCLUSIONS

A preliminary animal model of human craniopharyngioma was established in the nude mouse by heterotopic implantation. Surviving xenografts maintained their vascularization and proliferation activities until harvesting at 12 weeks.

摘要

目的

颅咽管瘤是鞍区和鞍上区最常见的先天性肿瘤之一,占所有颅内肿瘤的4%至6%。其肿瘤发生和生物学行为尚未得到充分研究,也未建立细胞系或动物模型。为了更好地了解该肿瘤并改善其临床管理,作者研究了将人类肿瘤细胞植入无胸腺裸鼠获得的皮下颅咽管瘤异种移植瘤中的血管生成和细胞增殖情况。

方法

将手术标本中获取的人类颅咽管瘤细胞皮下植入BALB/c-nu/nu裸鼠,建立移植瘤的初步动物模型。采用链霉亲和素-过氧化物酶复合物免疫组织化学染色法鉴定细胞表型,并评估异种移植瘤中的血管生成和增殖情况。通过计算机辅助显微镜定量检测异种移植瘤切片上细胞角蛋白、微小染色体维持缺陷6(MCM6)蛋白和内皮细胞标志物CD34的表达。15只裸鼠中获得了27个存活的皮下异种移植瘤。总植入成功率为28.12%(金刚烷上皮瘤[AE],37.50%;鳞状乳头瘤[SPT],18.75%)。在所有这些异种移植瘤中均观察到毛细血管形成和细胞增殖。存活移植瘤中微血管密度与MCM6免疫染色程度呈正相关(r = 0.410,p < 0.05),但AE组和SPT组在这些变量上无显著差异(p > 0.05)。

结论

通过异位植入在裸鼠中建立了人类颅咽管瘤的初步动物模型。存活的异种移植瘤在12周收获前维持其血管化和增殖活性。

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