Identification of novel pathways involved in the pathogenesis of human adamantinomatous craniopharyngioma.

Acta Neuropathologica
Cynthia L AndoniadouJuan P Martinez-Barbera

Abstract

Activating mutations in the gene encoding β-catenin have been identified in the paediatric form of human craniopharyngioma (adamantinomatous craniopharyngioma, ACP), a histologically benign but aggressive pituitary tumour accounting for up to 10% of paediatric intracranial tumours. Recently, we generated an ACP mouse model and revealed that, as in human ACP, nucleocytoplasmic accumulation of β-catenin (β-cat(nc)) and over-activation of the Wnt/β-catenin pathway occurs only in a very small proportion of cells, which form clusters. Here, combining mouse genetics, fluorescence labelling and flow-sorting techniques, we have isolated these cells from tumorigenic mouse pituitaries and shown that the β-cat(nc) cells are enriched for colony-forming cells when cultured in stem cell-promoting media, and have longer telomeres, indicating shared properties with normal pituitary progenitors/stem cells (PSCs). Global gene profiling analysis has revealed that these β-cat(nc) cells express high levels of secreted mitogenic signals, such as members of the SHH, BMP and FGF family, in addition to several chemokines and their receptors, suggesting an important autocrine/paracrine role of these cells in the pathogenesis of ACP and a reciprocal comm...Continue Reading

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Citations

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Datasets Mentioned

BETA
E-MEXP-3492

Methods Mentioned

BETA
flow cytometry
PCR
nuclear translocation

Software Mentioned

Leica
ArrayExpress
LAS AF
Definiens Developer XD1
Summit

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