Angiogenesis and cell proliferation in human craniopharyngioma xenografts in nude mice

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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.

Abbreviations used in this paper:AE = adamantine epithelioma; CK = cytokeratin; MCM6 = minichromosome maintenance deficient 6; MVD = microvessel density; SPT = squamous papillary tumor.

Article Information

Address reprint requests to: Chao You, M.D., Ph.D., Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China. email: Jianguo_1229@sina.com.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Photomicrographs demonstrating cellular proliferation in xenografts.Upper: Active proliferation is visible in AE xeno-graft cells. The actively proliferating nuclei were intensely immunostained with anti-MCM6 in cell nests; staining was relatively infrequent in the stellate reticulum.Lower: Proliferation in SPT xenograft cells. Most of the cells that were intensely immunostained with anti-MCM6 were dispersed in squamous epithelial layers. The nuclear reaction product of MCM6 was sparsely expressed in loose connective tissue. Immunoperoxidase, original magnifications × 325(upper) and × 400(lower).

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    Photomicrographs showing xenograft vascularization.Upper: Microvessels labeled by CD24 are visible in a section from an AE xenograft. Angiogenesis was evident in the stroma near enamel epithelial layers.Lower: Two capillaries stained by CD34 are visible in this section from the center of an SPT xenograft. Immunoperoxidase, original magnification × 400.

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