Angiogenesis and cell proliferation in human craniopharyngioma xenografts in nude mice

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.