Naslov
The role of WNT signaling pathway and epithelial-mesenchymal transition in intracranial meningiomas

Autori
Bukovac, Anja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, ostalo, znanstveni

Skup
EuroSciCon - Advancing pathology for cancer diagnosis, staging and prognosis

Mjesto i datum
Online, 16.10.2017

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
WNT signaling pathway, epithelial-mesenchymal transition, intracranial meningiomas

Sažetak
The Wnt signaling pathway, is one of the basic cellular pathways essential during the embryonic development and also suspected to have a role in meningioma tumorigenesis. Epithelial to mesenchymal transition (EMT) plays an important role in the tumor invasion and metastasis. Classical Wnt pathway has a tight link with EMT and it has been shown that nuclear translocation of beta-catenin can induce EMT. The most prominent feature of EMT is the so called cadherin switch in which loss of expression of E-cadherin - protein marker of epithelial cells, is accompanied with the increased expression of N-cadherin and the acquisition of mesenchymal phenotype. The expression of E-cadherin is recorded in morphologically benign tumors and is lost with the development of malignancy and metastasis. Identifying the molecular changes responsible for the control of cell motility and invasion brings potential markers of progression and reveals new molecular targets for therapeutic intervention. Therefore, the aim of this study was to investigate the potential role of cadherin switch and consequently Wnt signaling pathway in progression of invasive intracranial meningiomas. In order to do so, we analyzed genetic changes of E-cadherin gene (CDH1) and protein expression of N-cadherin in 45 samples of human meningioma with different grades of malignancy. Also we examined protein expression and localization of beta-catenin. Genetic alternations of CDH1 gene (loss of heterozygosity, microsatellite instability) were tested by polymerase chain reaction (PCR) using microsatellite marker D16S3025 and analyzed by electrophoresis on Spreadex gels. Expression and localization of N-cadherin and beta-catenin was detected using DAB-labeled immunohistochemical reaction (EnVisionTM, Dako REALTM) and specific monoclonal antibody for N- cadherin (D-4: sc-8424, Santa Cruz Biotechnology, Inc.) and beta-catenin (Monoclonal Mouse Anti-Human Beta-Catenin Clone b-Catenin-1 Code M3539, Dako) on paraffin- embedded meningioma sections followed by image analysis (ImageJ – NIH, NCI, Bethesda MD, USA). Image analysis revealed 71% of meningioma samples with moderate expression levels of N- cadherin, 13% with strong, while only 16% demonstrated weak N-cadherin expression. The results on CDH1 changes showed that genetic changes of E-cadherin were present in 18% of meningioma. Preliminary results of beta-catenin staining showed that it was progressively upregulated from meningothelial to atypical, while 60% of anaplastic showed upregulation and nuclear localization of the protein. All our findings suggest involvement of cadherin switch and canonical Wnt signaling pathway in meningioma.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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