Project Details
Projekt
The pathogenesis of craniopharyngiomas: Characterization of a tumor stem cell niche as a target for novel treatment strategies
Applicant
Professor Dr. Rolf Buslei
Subject Area
Endocrinology, Diabetology, Metabolism
Clinical Neurology; Neurosurgery and Neuroradiology
Molecular and Cellular Neurology and Neuropathology
Clinical Neurology; Neurosurgery and Neuroradiology
Molecular and Cellular Neurology and Neuropathology
Term
from 2014 to 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 262710192
Adamantinomatous craniopharyngiomas (adaCP) are difficult to treat epithelial tumors of the sellar region, with clinical signs of visual-, endocrinological- and cognitive disorders. They represent one of the most frequent brain tumors in children with characteristic finger like protrusions into the surrounding brain structures (e.g. optic chiasm, pituitary and hypothalamus). This distinct growth pattern makes complete surgical removal often difficult to obtain without causing additional brain injury. Tumor remnants show a high frequency of regrowth and even in cases with complete surgical removal recurrence rates up to 20% are described. Therefore, post-surgical radiotherapy is performed in cases of partial resection. Late effects after radiation therapy in children are often particularly pronounced leading to complete pituitary insufficiency and Diabetes insipidus in several cases. A better understanding of the underlying cells and mechanisms causing tumor growth and recurrence would be very important to establish appropriate treatment options and target oriented treatment strategies. In previous studies we were able to show the impact of Wnt- and EGFR- signaling pathways on the morphology and the growth pattern of adaCP. Using Gefitinib, a tyrosin-kinase inhibitor, we were already able to significantly reduce tumor cell migration in vitro, an effect that remains to be shown in vivo. Furthermore, we described the existence of a tumor stem cell niche within adaCP, a finding that was recently supported in a newly developed mouse model. In the presented application we would like to further characterize these peculiar cell clusters, analyze their tumorigenic potential and the impact on tumor outgrowth in adaCP. To achieve these objectives, we have successfully developed a novel xenograft mouse model which enables as in vivo testing. We expect that our results will provide important basic principles in the development of new prognostic markers and target oriented treatment options for craniopharyngiomas.
DFG Programme
Research Grants
