FIGURE 3.

Schematic showing a working model for the role of the β‐catenin‐accumulating cell clusters in mouse and human ACP. (A) Expression of oncogenic β‐catenin in SOX2+ pituitary stem cells (both embryonic and postnatal) results in the formation of β‐catenin‐accumulating cell clusters, which contain senescent cells (oncogene‐induced senescence). Senescent cluster cells activate a senescence‐associated secretory phenotype (SASP), which leads to the synthesis and secretion of a plethora of active peptides, some of which are included in the box. The persistent activity of the SASP factors on surrounding cells eventually causes cell transformation of a cell not of the SOX2 cell lineage (purple cell) and subsequent tumour development in a paracrine manner. (B). The human tumour depicted in the schematic derives from a three‐dimensional reconstruction of a micro‐CT‐imaged human ACP sample, in which the glial reactive tissue has not been rendered. Purple indicates the stellate reticulum and cells of the palisading epithelium, and green represents the β‐catenin‐accumulating cell clusters. Note the presence of finger‐like protrusions of tumour cells, which project away from a tumour epithelium mass, containing a string of clusters inside. These human clusters are molecularly analogous to the mouse clusters and share a signature of senescence and SASP. The model proposes that the SASP activities underlie tumour growth and invasive behaviour by promoting epithelial remodelling and proliferation. Reproduced with permission from S. Karger AG, Basel (Martinez‐Barbera J. P. and Andoniadou C. L., Biological Behaviour of Craniopharyngiomas. Neuroendocrinology 2020. https://doi.org/10.1159/000506904)