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CANCER STEM CELLS AND
ONCOLOGY RESEARCH
11
th
International Conference on
Journal of Medical Oncology and Therapeutics
|
Volume 3
Anja Bukovac et al., J Med Oncl Ther 2018, Volume 3
INVOLVEMENT OF N-, E-CADHERIN
AND BETA-CATENIN IN PROGRESSION
OF INTRACRANIAL MENINGIOMA
Anja Bukovac
1
, Anja Kafka
1
, Andreas Tomić
1
, Petar Brlek
1
,
Davor Tomas
1,2
and
Nives Pećina-Šlaus
1
1
University of Zagreb, Croatia
2
Sisters of Charity Hospital, Croatia
T
he majority of intracranial meningiomas are benign primary tumors.
However, 20% are classified as atypical (grade II) and anaplastic
(grade III) showing aggressive character and higher probability of
recurrence. We believe that such an invasive character of meningioma
subtypes could be explained due to the epithelial-mesenchymal transition
(EMT) and the activation of canonical Wnt signaling pathway. The
malfunctioning of Wnt signaling has been found in many human tumors
and many key molecules of Wnt pathway are also involved in EMT. EMT
is a biological process necessary for tumor invasion, during which cells
undergo molecular changes, become motile and metastasize. During
EMT, cells show the so called “cadherin switch” which is characterized
by loss of expression of E-cadherin - protein marker of epithelial cells,
and by increased expression of N-cadherin followed by the acquisition
of mesenchymal phenotype. Therefore, the aim of this study was to
investigate if main actors of EMT and canonical Wnt signaling pathway
are affected in progression of intracranial meningiomas and to identify
potential markers for the control of cellular mobility. In order to do so, we
analyzedproteinexpressionand localizationofN-cadherin, E-cadherinand
beta-catenin in 50 samples of human meningioma with different grades
of malignancy. Expression and localization of proteins was investigated
using DAB-labeled immunohistochemistry (EnVisionTM, Dako REALTM)
and specific monoclonal antibodies for N-cadherin, E-cadherin and beta-
catenin on paraffin-embedded meningioma sections. Image analysis
(ImageJ – NIH, NCI, Bethesda MD, USA) was also used. For the purpose
of identifying the subcellular localization and levels of expression, 200
cells of tumor hot spots were selected and counted. Also, we tested if the
expression of E-cadherin protein was influenced by genetic alternations
of its CDH1 gene. This was studied by polymerase chain reaction (PCR)/
loss of heterozygosity (LOH) or microsatellite instability (MSI) analyses
using microsatellite marker D16S3025. Our results demonstrated
that the majority of meningioma samples (70%) showed moderate
expression levels of N-cadherin. Beta-catenin was upregulated and
transferred to the nucleus in 71.2% of meningiomas which is indicative
of the pathway activation. The results on CDH1 genetic changes showed
that 9% of meningiomas harbored LOH, 13% showed MSI and 4% of
Anja Bukovac is currently persuing her Phd at
the Laboratory of Neurooncology, Croatian In-
stitute for Brain Research, School of Medicine
University of Zagreb, Zagreb, Croatia.
anja.bukovac@mef.hrBIOGRAPHY
them showed both LOH and MSI. In patients
who demonstrated CDH1 genetic changes
moderate expression levels of E-cadherin
protein were observed. The higher percent
of observed MSI could be explained by our
previous study (Pećina-Šlaus et al., Tumour
Biol. 2017; 39(7):1010428317705791.) where
we showed constant presence of MSI and
alterations of mismatch repair genes MLH1
and MSH2 in our collection of meningioma
patients. After additional future analyses
our findings could be useful as potential
biomarkers of cellular mobility of invasive
intracranial meningiomas.