engleski

Potential role of cadherin switch in progression of intracranial meningioma

One of the most common primary brain tumors are intracranial meningiomas, derived from arachnoidal cap cells and classified within 3 different malignancy grades. Although they are mostly considered as benign tumors with a share of approximately 80% of all meningiomas and classified as WHO grade I, remaining 20% are classified as atypical (grade II) and anaplastic (grade III) showing aggressive character and higher probability of recurrence. Epithelial-mesenchymal transition (EMT) is biological process necessary for embryogenesis but also involved in tumor invasion. During EMT cells undergo molecular changes and become motile. 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. Therefore, the aim of this study was to investigate the potential role of cadherin switch in progression of invasive intracranial meningiomas and identify potential markers of the molecular changes responsible for the control of cellular mobility. 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. 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 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.) on paraffin-embedded meningioma sections followed by image analysis (ImageJ – NIH, NCI, Bethesda MD, USA). Image analysis revealed the cellular localization and levels of N-cadherin expression in 200 cells of tumor hot spots. We have demonstrated 66, 7% of meningioma samples with moderate expression levels of N-cadherin, 30% with strong, while only 3, 3% demonstrated weak N-cadherin expression. The results on CDH1 changes showed that genetic changes of E- cadherin were present in a portion of meningioma. Moreover, we have found the presence of microsatellite instability in a noteworthy number of patients. Our results have shown that N-cadherin is strongly expressed, mostly in the cytoplasm. The findings are indicative on the involvement of cadherin switch in meningioma.

E-cadherin, N-cadherin, cadherin switch, meningioma, EMT

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