Insights into the Infiltrative Behavior of Adamantinomatous Craniopharyngioma in a New Xenotransplant Mouse Model

We describe a reproducible intracranial xenograft model of human adaCP which allows analysis of the entire tumor growth pattern, as well as invasion of adjacent brain regions

Christina Stache

2014

Scholarcy highlights

  • Craniopharyngiomas are benign epithelial brain tumors which arise from embryonic remnants of Rathke's pouch epithelium 3
  • AdaCP migration potential is enhanced by Wnt and epidermal growth factor receptor signaling 22, 23, which is activated in whirl‐like cell clusters displaying distinct nuclear β‐catenin accumulations
  • To reduce the chance of tumor relapse, subtotal resection is often accompanied by adjuvant radiotherapy; which can lead to treatment‐associated side effects 29
  • High resolution Magnetic resonance imaging performed at 4.7 Tesla enabled 3D reconstruction of a subset of xenografts, illustrating a typical CP growth pattern with micro finger‐shaped tumor protrusions into adjacent brain areas in accordance with histological processing
  • We have previously shown that β‐catenin accumulating cell clusters with activated EGFR are responsible for adaCP tumor cell migration
  • The β‐catenin accumulating cells within the whirl‐like structures may comprise cells that invade the brain either in a cell‐autonomous manner or they may direct other cells non‐cell autonomously by secretion of cytokines 3, 4. The suggestion that these cells may promote tumor cell migration, and represent the propulsive power of adaCP outgrowth is difficult to ascertain from human tumor samples
  • Examination of whole tumor transplants in serial sections revealed whirl‐like cell clusters with activated Wnt and epidermal growth factor receptor signaling pathways as the propulsive power of tumor outgrowth, displaying targets for future treatment strategies

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