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Potential target therapy in meningiomas: role of Dkk-3 and claudin-5
EANS Academy. Caffo M. Sep 27, 2019; 276091; EP04029
Abstract
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Meningiomas are the most common tumors of the CNS. The histological grading is the most impor­tant prognostic factor. The Dkk-3 protein is involved in embryonic develop­ment through its interactions with the Wnt pathway. Over-expression of Dkk-3 cause reduced cell proliferation and invasion. The REIC/Dkk-3 expression has been shown to be down-regulated in various cancer cell lines. Claudin-5 is a membrane protein which plays a role in the regulation of tumor cell motility. The aim of this study is to demonstrate the role of the Dkk-3 and claudin-5 in meningiomas of different histotype.
We evaluated Dkk-3 and claudin-5 expression in 30 tumors biopsies assessing both immunohistochemistry and western blotting. The expression strength was analyzed and graded based on the positive ratio and intensity of immunoreactivity. The molec­ular analyses were performed on frozen sections of tumor tissue, by West­ern Blot method. Statistical analysis was also performed.
The expression of Dkk-3 protein and claudin-5 were decreased in meningioma samples compared to controls. Also immunohistochemistry shows a slight expression of Dkk-3 pro­tein in meningioma samples examined. Claudin-5 levels were inversely expressed in meningiomas with reduced levels compared to controls.
Our results show that Dkk-3 and claudin-5 are down-regulated. More, we demonstrated an alteration of the BBB and a decreasing of apoptotic susceptibility. The immunoreactivity of vascular neoplastic endothelium suggest a role in angiogenesis. These data could suggest a key role of Dkk-3 in the progression of meningiomas through its onco-suppressor potential. At the same time, the demonstration of the altered expression of claudin-5 confirms its protective role in modulating the integrity of the barrier, in response to an abnormal condition of neuronal cells due to the onset of the tumor. We suggest that the re-establishment of Dkk-3 expression can represent a new potential therapeutic approach in meningiomas treat­ment also by modulation of BBB permeability.
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