1 Departments of Neurosurgery and Medical Genetics, West China Hospital, Sichuan University; and Division of Human Morbid Genomics, State Key Laboratory of Biotherapy of Human Diseases, Chengdu, People’s Republic of China
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.
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).
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.
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:
El-AssalONYamanoiASodaYYamaguchiMIgarashiMYamamotoA: Clinical significance of microvessel density and vascular endothelial growth factor expression in hepato-cellular carcinoma and surrounding liver: possible involvement of vascular endothelial growth factor in the angiogenesis of cirrhotic liver. Hepatology27:1554–15621998
GoldbergGMEshbaughDE: Squamous cell nests of the pituitary gland as related to the origin of craniopharyngiomas. A study of their presence in newborns and infants to age four. Arch Pathol70:293–2991960
HuangPTaghianAAllamAFreemanJDuffyMSuitH: The effect of whole-body irradiation of nude mice on the tumor transplantability and control probability of a human soft tissue sarcoma xenograft. Radiat Res145:337–3421996
MéndezJStillmanB: Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis. Mol Cell Biol20:8602–86122000
SchraderCJanssenDKlapperWSiebmannJUMeusersPBrittingerG: Minichromosome maintenance protein 6, a proliferation marker superior to Ki-67 and independent predictor of survival in patients with mantle cell lymphoma. Br J Cancer93:939–9452005
StrippDCMaityAJanssAJBelascoJBTochnerZAGoldweinJW: Surgery with or without radiation therapy in the management of craniopharyngiomas in children and young adults. Int J Radiat Oncol Biol Phys58:714–7202004