Az epidermal growth factor receptorok és az integrinek tumorinvázióban betöltött szerepének vizsgálata intrakraniális daganatokban = Investigation of the role of epidermal growth factor receptors and integrins in the tumor invasion of intracranial tumors

Intraoperative gyorsfagyasztott szövetminták katalogizált, hosszú távú biztonságos tárolása céljából az OTKA támogatás segítségével létrehoztuk a Debreceni Idegsebészeti Agydaganat- és Szövetbankot. 2005. december és 2008. december között kb. 612 műtétből közel 3000 tumormintát, 290 betegből 1140 szérummintát gyűjtöttünk. Az így kialakított tumorbankra épülve saját kutatásokat indítottunk, ill. számos kutatóintézettel léptünk aktív kollaborációra. Kutatásaink során vizsgáltuk a daganatos invázióban résztvevő extracelluláris mátrix komponensek mRNS expresszióját, kiegészítve a releváns molekulák immunhisztokémiai (IHC) és western-blot vizsgálatával. Nyolc szövettanilag különböző mintacsoportban összesen 93 gén mRNS expresszióját vizsgáltuk. Különböző eredetű intracerebrális daganatok extracelluláris mátrixának összehasonlító elemzése során összesen 22 molekula mutatott szignifikáns különbséget. Az intracerebralis daganatok progressziójában szerepet játszó sejtfelszíni receptorok közül az EGFR, az integrin receptorcsalád, és legfontosabb ligandjaik, a kollagének, a fibronektin és a lamininek mRNS expresszióját vizsgáltuk. Az EGFR amplifikációt FISH-sel, az EGFRvIII mutációt IHC-val, az EGFR és az integrin B1 sejtfelszíni expresszióját konfokális mikroszkópiával, a receptorok kolokalizációját pedig flow-cytometriával hatátoztuk meg. A különböző eredetű intracerebrális daganatok összehasonlító elemzése során összesen 17 molekula mutatott szignifikáns különbséget. | The Neurosurgical Tumor and Tissue Bank of Debrecen was established in 2005 by the financial support of OTKA. Tissue samples were collected intraoperative, frozen immediately and stored at -80oC for providing good quality long lasting samples for researches. Between December 2005 and 2009 more than 3000 tissue samples were collected from 612 operations and 1140 serum samples from 290 patients. Samples of the Tumor and Tissue Bank were used for own researches and for collaborations with other laboratories. In our studies the mRNA expression of extracellular matrix (ECM) molecules was investigated and immunohistochemical (IHC) determination of the relevant molecules as well as Western-blot analysis were performed. Ninety-three genes were evaluated in eight histological different groups of tissue samples. Comparing the ECM molecules of intracerebral tumors from different origin twenty-two molecules showed significant differences. The mRNA expression of transmembrane receptors that play pivotal role in tumor progression and invasion (epidermal growth factor receptors - EGFRs, integrins) and their ligands (laminins, collagens and fibronectin) were also investigated by QRT-PCR, EGFR amplification was tested by FISH and EGFRvIII mutation by IHC. EGFR and integrin expression on cell surface and their co-localization were evaluated by confocal microscopy and flow-cytometry. By comparison of tumors from different origin, significant differences were found in case of 17 molecules

Small Extracellular Vesicles Isolated from Serum May Serve as Signal-Enhancers for the Monitoring of CNS Tumors

L

PRMT1 and PRMT8 regulate retinoic acid-dependent neuronal differentiation with implications to neuropathology

Retinoids are morphogens and have been implicated in cell fate commitment of embryonic stem cells (ESCs) to neurons. Their effects are mediated by RAR and RXR nuclear receptors. However, transcriptional co-factors required for cell and gene-specific retinoid signaling are not known. Here we show that Protein aRginine Methyl Transferase (PRMT) 1 and 8 have key roles in determining retinoid regulated gene expression and cellular specification in a multistage neuronal differentiation of murine ESCs. PRMT1 acts as a selective modulator, providing the cells with a mechanism to reduce the potency of retinoid signals on regulatory "hotspots". PRMT8 is a retinoid receptor target gene itself and acts as a cell type specific transcriptional co-activator of retinoid signaling at later stages of differentiation. Lack of either of them leads to reduced nuclear arginine methylation, dysregulated neuronal gene expression and altered neuronal activity. Importantly, depletion of PRMT8 results in altered expression of a distinct set of genes, including markers of gliomagenesis. PRMT8 is almost entirely absent in human glioblastoma tissues. We propose that PRMT1 and PRMT8 serve as a rheostat of retinoid signaling to determine neuronal cell specification in a context- dependent manner, and might also be relevant in the development of human brain malignancy

Significance of liquid biopsy in glioblastoma – A review

L

Significance of liquid biopsy in glioblastoma: a review

L