gms | German Medical Science

Question: Adamantinomatous craniopharyngiomas (adaCP) are histological benign epithelial tumors of the sellar region, causing severe endocrinological deficits by invading the pituitary gland and the hypothalamus. Current treatment options are limited rendering the molecular pathobiology of adaCP to be elucidated. Herein, we generated a first in vivo brain tumor model of human adaCP in order to be able to study underlying pathomechanisms of tumor development and progression and to test new pharmacological treatment strategies.

Methods: Human primary adaCP cells (50x10³ – 150x10³) were obtained from three different surgical specimens and stereotactically implanted into the brain of six week old NMRI ^nu/nu - mice (8 females, 12 males; n=20). Sham treated control mice (n=6) received phosphate buffered saline injections. All animals obtained analgetic treatment for one week. Eleven weeks after tumor cell inoculation, all brain specimens were microscopically reviewed using haematoxylin/eosin as well as immunohistochemical stainings.

Results: Histology confirmed tumor growth in 6 out of 20 treated mice (30%). Tumors had an average diameter of 250 µm, were predominantly located subdural and showed histological hallmarks of human adaCP including calcifications, wet keratin and whirl-like cell clusters. Immunohistochemistry displayed proliferating tumor cells (Ki67) with distinct cytokeratin expression (KL1) and cells with nuclear β-catenin accumulation. Only small scars with hemosiderin deposits but no tumors were observed in any of the control animals.

Conclusion: To the best of our knowledge, here we present a first animal model of human craniopharyngiomas in brains of nude mice applying heterotopic human tumor cell implantation. Transplanted cells generated solid tumors with histomorphological and immunohistochemical hallmarks of human adaCP. This in vivo mouse model is promising to study growth characteristics and assess novel drug targets of human adaCP.