P Brlek1,2, A Bukovac1,2, A Kafka1,2, N Pećina-Šlaus3,4. 1. Department of Biology, School of Medicine, University of Zagreb, Šalata 3, 10000, Zagreb, Croatia. 2. Laboratory of Neurooncology, Croatian Institute for Brain Research School of Medicine, University of Zagreb, Šalata 12, 10000, Zagreb, Croatia. 3. Department of Biology, School of Medicine, University of Zagreb, Šalata 3, 10000, Zagreb, Croatia. nina@mef.hr. 4. Laboratory of Neurooncology, Croatian Institute for Brain Research School of Medicine, University of Zagreb, Šalata 12, 10000, Zagreb, Croatia. nina@mef.hr.
Abstract
PURPOSE: E-cadherin is a calcium-dependent glycoprotein whose main role is cell-cell adhesion. Its transcriptional repressor TWIST1 is a basic helix-loop-helix (bHLH) protein that participates in gastrulation and formation of mesodermal tissues during embryogenesis. In adult tissues, the high expression of TWIST1 induces the epithelial-mesenchymal transition (EMT)-a process in which cells become motile and able to metastasize. In this paper, we investigated the involvement of E-cadherin and TWIST1 in the carcinogenesis of brain metastases originating from two different primary sites-breast and lung. METHODS: The localization and expression of E-cadherin and its transcriptional repressor TWIST1 were investigated using a DAB-labeled streptavidin-horseradish peroxidase immunohistochemical reaction and specific monoclonal antibodies against TWIST1 and E-cadherin. Image J software was used for semi-quantitative analysis while H-score served for statistical evaluations. RESULTS: Immunohistochemistry showed that the expression of E-cadherin was downregulated in 85.7% of brain metastases, while at the same time, 82.2% of them showed upregulated TWIST1. Statistical analysis confirmed a significant negative correlation between expressions of TWIST1 and E-cadherin (p = 0.001). When the brain metastases expression levels were compared to primary breast tumors in corresponding patients, E-cadherin showed higher expression in primary pairs compared to corresponding metastases. Consistent to its role, TWIST1 was downregulated in all primary tumor samples in comparison to corresponding metastases pairs (p = 0.034). CONCLUSION: This research provides valuable data regarding molecular events involving two EMT key components that could give directions for new possibilities for brain metastases diagnosis and treatment.
PURPOSE: E-cadherin is a calcium-dependent glycoprotein whose main role is cell-cell adhesion. Its transcriptional repressor TWIST1 is a basic helix-loop-helix (bHLH) protein that participates in gastrulation and formation of mesodermal tissues during embryogenesis. In adult tissues, the high expression of TWIST1 induces the epithelial-mesenchymal transition (EMT)-a process in which cells become motile and able to metastasize. In this paper, we investigated the involvement of E-cadherin and TWIST1 in the carcinogenesis of brain metastases originating from two different primary sites-breast and lung. METHODS: The localization and expression of E-cadherin and its transcriptional repressor TWIST1 were investigated using a DAB-labeled streptavidin-horseradish peroxidase immunohistochemical reaction and specific monoclonal antibodies against TWIST1 and E-cadherin. Image J software was used for semi-quantitative analysis while H-score served for statistical evaluations. RESULTS: Immunohistochemistry showed that the expression of E-cadherin was downregulated in 85.7% of brain metastases, while at the same time, 82.2% of them showed upregulated TWIST1. Statistical analysis confirmed a significant negative correlation between expressions of TWIST1 and E-cadherin (p = 0.001). When the brain metastases expression levels were compared to primary breast tumors in corresponding patients, E-cadherin showed higher expression in primary pairs compared to corresponding metastases. Consistent to its role, TWIST1 was downregulated in all primary tumor samples in comparison to corresponding metastases pairs (p = 0.034). CONCLUSION: This research provides valuable data regarding molecular events involving two EMT key components that could give directions for new possibilities for brain metastases diagnosis and treatment.
Authors: Krzysztof Marek Mrozik; Orest William Blaschuk; Chee Man Cheong; Andrew Christopher William Zannettino; Kate Vandyke Journal: BMC Cancer Date: 2018-10-01 Impact factor: 4.430
Authors: Asad Ur Rehman; Parvez Khan; Shailendra Kumar Maurya; Jawed A Siddiqui; Juan A Santamaria-Barria; Surinder K Batra; Mohd Wasim Nasser Journal: Mol Cancer Date: 2022-05-10 Impact factor: 41.444