engleski

Epithelial-to-mesenchimal transition: possible role in meningiomas

Epithelial to mesenchimal transition (EMT) is a process very much involved in invasion and metastasis of tumors. The occurence of EMT during tumor progression resembles the developmental scenario and sheds light on important mechanisms for the initial step of metastasis – invasion where noninvasive tumor cells acquire motility and ultimately disseminate to organs distant from the primary site. The hallmark of EMT is the loss of expression of the cell-cell adhesion molecule E-cadherin. The numerous reports by many authors as well as our own results indicate that E-cadheirn plays a role in CNS tumors - meningiomas. Our studies on meningiomas of different grades showed that 73% of meningiomas had downregulation of E-cadherin expression. Intense downregulation was noticed in tumors with grades II and III. Our analysis on the genetic level of E-cadherin changes showed loss of heterozygosity (LOH) in 32% meningiomas investigated. Bound to E-cadherin in adherens junctions is beta-catenin, the main effector molecule in wnt signaling whose translocation to the nucleus is yet another molecular event involved in EMT. In our study beta-catenin was progressively upregulated from meningothelial to atypical, while 60% of anaplastic meningiomas showed upregulation and nuclear localization of the protein. A significant association between the genetic changes of E-cadherin and the nuclear localization of beta-catenin protein was established (P<0.022). The suppression of E-cadherin expression is regarded as one of the main molecular events responsible for EMT. The elucidation of molecular mechanisms that govern EMT will offer new approaches and targets to restrain metastasis.

e-cadherin ; Epithelial to mesenchimal transition

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