Preclinical transgenic and patient-derived xenograft models recapitulate the radiological features of human adamantinomatous craniopharyngioma.
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Embargo End Date
ICR Authors
Authors
Boult, JKR
Apps, JR
Hölsken, A
Hutchinson, JC
Carreno, G
Danielson, LS
Smith, LM
Bäuerle, T
Buslei, R
Buchfelder, M
Virasami, AK
Koers, A
Arthurs, OJ
Jacques, TS
Chesler, L
Martinez-Barbera, JP
Robinson, SP
Apps, JR
Hölsken, A
Hutchinson, JC
Carreno, G
Danielson, LS
Smith, LM
Bäuerle, T
Buslei, R
Buchfelder, M
Virasami, AK
Koers, A
Arthurs, OJ
Jacques, TS
Chesler, L
Martinez-Barbera, JP
Robinson, SP
Document Type
Journal Article
Date
2018-07-01
Date Accepted
2017-04-18
Abstract
To assess the clinical relevance of transgenic and patient-derived xenograft models of adamantinomatous craniopharyngioma (ACP) using serial magnetic resonance imaging (MRI) and high resolution post-mortem microcomputed tomography (μ-CT), with correlation with histology and human ACP imaging. The growth patterns and radiological features of tumors arising in Hesx1Cre/+ ;Ctnnb1lox(ex3)/+ transgenic mice, and of patient-derived ACP xenografts implanted in the cerebral cortex, were monitored longitudinally in vivo with anatomical and functional MRI, and by ex vivo μ-CT at study end. Pathological correlates with hematoxylin and eosin stained sections were investigated. Early enlargement and heterogeneity of Hesx1Cre/+ ;Ctnnb1lox(ex3)/+ mouse pituitaries was evident at initial imaging at 8 weeks, which was followed by enlargement of a solid tumor, and development of cysts and hemorrhage. Tumors demonstrated MRI features that recapitulated those of human ACP, specifically, T1 -weighted signal enhancement in the solid tumor component following Gd-DTPA administration, and in some animals, hyperintense cysts on FLAIR and T1 -weighted images. Ex vivo μ-CT correlated with MRI findings and identified smaller cysts, which were confirmed by histology. Characteristic histological features, including wet keratin and calcification, were visible on μ-CT and verified by histological sections of patient-derived ACP xenografts. The Hesx1Cre/+ ;Ctnnb1lox(ex3)/+ transgenic mouse model and cerebral patient-derived ACP xenografts recapitulate a number of the key radiological features of the human disease and provide promising foundations for in vivo trials of novel therapeutics for the treatment of these tumors.
Citation
Brain pathology (Zurich, Switzerland), 2018, 28 (4), pp. 475 - 483
Source Title
Publisher
WILEY
ISSN
1015-6305
eISSN
1750-3639
Research Team
Paediatric Solid Tumour Biology and Therapeutics
Pre-Clinical MRI
Pre-Clinical MRI