TWIST1 upregulation affects E-cadherin expression in brain metastases

Autor: Anja Bukovac, Petar Brlek, Nives Pećina-Šlaus, Anja Kafka
Rok vydání: 2020
Předmět:
0301 basic medicine
Adult
Male
Cancer Research
animal structures
Lung Neoplasms
medicine.drug_class
Nuclear Proteins / physiology
Breast Neoplasms
medicine.disease_cause
Monoclonal antibody
Cadherins / biosynthesis
Lung Neoplasms / pathology
Metastasis
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
medicine
Humans
Epithelial–mesenchymal transition
Aged
Aged
80 and over
business.industry
Cadherin
Brain Neoplasms
Twist-Related Protein 1
Nuclear Proteins
General Medicine
Breast Neoplasms / pathology
Middle Aged
medicine.disease
Cadherins
Primary tumor
Twist-Related Protein 1 / physiology
Up-Regulation
metastasis
brain
epithelial-mesenchymal transition
TWIST1
E-cadherin
030104 developmental biology
Brain Neoplasms / secondary
Oncology
030220 oncology & carcinogenesis
Brain Neoplasms / metabolism
Cancer research
Immunohistochemistry
Female
Carcinogenesis
business
Zdroj: Clinicaltranslational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 23(6)
ISSN: 1699-3055
Popis: 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.
Databáze: OpenAIRE
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