PRKCA, PTPN1 and ZYX Are Possible Markers to Target CD133+ GBM Stem Cells

Abstract

IntroductionGlioblastoma Multiforme (GBM) accounts for more than %75 of malignant brain tumors. GBM stem cells (GSCs) have a crucial role in tumor formation, development, chemo‐resistance and recurrence. CD133, the first discovered cell surface marker for GBM, is a pentaspan transmembrane glycoprotein. In this study, it is aimed to investigate new therapeutic targets within cell adhesion molecules to select and eliminate CD133+ GSCs effectively.MethodsTen primary GBM cells were isolated from freshly obtained GBM tissue samples and they were cultured. CD133+ and CD133− cells were seperated by MACS method via anti‐CD133 (AC133) antibody from those GBM primary cells and cell lines. Following RNA isolation from CD133 positive and negative cells, cDNA synthesis was performed. Finally, by applying micro array protocol for cell adhesion molecules, mRNA expression levels of 88 genes were detected. Proper results were collected and analysed statistically.ResultsAccording to the results of microarray; it has been found that CD133+ cells express 8,73 fold PRKCA, 2,17 fold PTPN1 and ZYX 5,29 fold when they are compared with CD133− cells.ConclusionsPRKCA (Protein Kinase C, Alpha) is a serine‐threonine kinase that regulates PI3K‐Akt pathway. This gene has been reported to have a role in proliferation, apoptosis, differentiation, migration and adhesion, angiogenesis and therefore tumorigenesis. It also activates MAPK pathway, which leads to cell proliferation.PTPN1 (Protein Tyrosine Phosphatase, Non‐receptor Type 1) is a tyrosine phosphatase. It dephosphorylates kinases like EGFR, JAK2 and TYK2. By inhibiting MAPK pathway PTPN1 promotes cell proliferation.ZYX (Zyxin) is a zinc‐binding phosphoprotein that concentrates at focal adhesions and along the actin cytoskeleton. It has a proline rich domain which may interact with SH3 domains of proteins that have a role in signaling pathways. Moreover, ZYX has a role in cell migration. High expressions of zyxin might mean higher motility of malignant tumors and therefore tumor initiation, progression and metastasis.To conclude, since PRKCA, PTPN1 and ZYX are related with tumorigenesis and malignant cell motility, and are highly expressed on GBM CD133+ cells, it seems that PRKCA, PTPN1 and ZYX may be essential markers to target CD133+ GBM stem cells.Support or Funding InformationThis research has been supported by The Scientific and Technological Research Council of Turkey (No:114S189)