Abstract
Although GH- and PRL-secreting pituitary adenomas are considered benign, in many patients, tumor growth and/or invasion constitute a particular challenge. In other tumors, progression relies in part on dysfunction of intercellular adhesion mediated by the large family of cadherins. In this study, we have explored the contribution of cadherins in GH and PRL adenoma pathogenesis, and evaluated whether this class of adherence molecules was related to tumor invasiveness. We have first established, by qPCR and immunohistochemistry, the expression profile of classical cadherins in normal human pituitary gland. We show that the cadherin repertoire is restricted and cell-type specific. Somatotrophs and lactotrophs express mainly E-cadherin and cadherin 18, while N-cadherin is present in the other endocrine cell types. This repertoire undergoes major differential modification in GH and PRL tumors: E-cadherin is significantly reduced in invasive GH adenomas, and this loss is associated with a cytoplasmic relocalization of cadherin 18 and catenins. In invasive prolactinomas, E-cadherin distribution is altered and is accompanied by a mislocalization of cadherin 18, beta-catenin and p120 catenin. Strikingly, de novo expression of N-cadherin is present in a subset of adenomas and cells exhibit a mesenchymal phenotype exclusively in invasive tumors. Binary tree analysis, performed by combining the cadherin repertoire with the expression of a subset of known molecular markers, shows that cadherin/catenin complexes play a significant role in discrimination of tumor invasion.
Original language | English |
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Article number | 26686489 |
Journal | Journal of Neuroendocrinology |
Volume | 28 |
Issue number | 2 |
Early online date | 20 Dec 2015 |
DOIs | |
Publication status | Published - Feb 2016 |
Keywords / Materials (for Non-textual outputs)
- Human pituitary tumors
- Cadherins
- Epithelial Mesenchymal Transition
- ESRP
- Binary tree analysis
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Nicola Romano
- Deanery of Biomedical Sciences - Senior Lecturer
- Centre for Discovery Brain Sciences
- Edinburgh Neuroscience
Person: Academic: Research Active