Untersuchung zur Wachstumshemmung humaner Meningeomzellen in athymen Nacktmäusen durch Behandlung mit Celecoxib

Abstract

Meningiomas are slow growing benign tumors of the central nervous system (CNS) and originate from the meninges. Primary goal of therapy is surgical resection, but numerous meningiomas with anatomical restraints need alternative therapeutic options. A promising approach is the treatment with cyclooxygenase-2 (COX-2) inhibitors. Several studies showed that the COX-2 inhibitor Celecoxib reduced growth of meningioma cells in vitro and in vivo in a subcutaneous heterotopic mouse model. However, so far no appropriate animal model was available to test the effect of Celecoxib in an intracranial orthotopic animal model. For this dissertation we investigated whether primary cell cultures of human meningiomas would show reliable and reproducible growth in an orthotopic animal model. Moreover, the histomorphology and immunohistology were compared to the original human tumors. It was shown that these tumors reliably grow intracranially in mice and that their histomorphological and immunohistological attributes are comparable to their human origin. The effect of Celecoxib on these meningiomas was tested in mice after intracranial transplantation and in cell cultures. Celecoxib inhibited the growth of meningiomas in cell culture, but it did not affect growth in mice. This animal model may be suitable to study the pathophysiology and pharmacology of human meningiomas. More generally, these studies show that with regard to brain tumors the results gathered with subcutaneous heterotopic animal models and in vitro experiments should not be generalized. With regard to brain tumors, the importance of using an intracranial orthotopic animal model for prospective pharmacological studies is highlighted.