20.500.12556/DiRROS-19881 Transmembrane protein CD9 is glioblastoma biomarker, relevant for maintenance of glioblastoma stem cells The cancer stem cell model suggests that glioblastomas contain a subpopulation of stem-like tumor cells that reproduce themselves to sustain tumor growth. Targeting these cells thus represents a novel treatment strategy and therefore more specific markers that characterize glioblastoma stem cells need to be identified. In the present study, we performed transcriptomic analysis of glioblastoma tissues compared to normal brain tissues revealing sensible up-regulation of CD9 gene. CD9 encodes the transmembrane protein tetraspanin which is involved in tumor cell invasion, apoptosis and resistance to chemotherapy. Using the public REMBRANDT database for brain tumors, we confirmed the prognostic value of CD9, whereby a more than two fold up-regulation correlates with shorter patient survival. We validated CD9 gene and protein expression showing selective up-regulation in glioblastoma stem cells isolated from primary biopsies and in primary organotypic glioblastoma spheroids as well as in U87-MG and U373 glioblastoma cell lines. In contrast, no or low CD9 gene expression was observed in normal human astrocytes, normal brain tissue and neural stem cells. CD9 silencing in three CD133+ glioblastoma cell lines (NCH644, NCH421k and NCH660h) led to decreased cell proliferation, survival, invasion, and self-renewal ability, and altered expression of the stem-cell markers CD133, nestin and SOX2. Moreover, CD9-silenced glioblastoma stem cells showed altered activation patterns of the Akt, MapK and Stat3 signaling transducers. Orthotopic xenotransplantation of CD9-silenced glioblastoma stem cells into nude rats promoted prolonged survival. Therefore, CD9 should be further evaluated as a target for glioblastoma treatment. biomarker CD9 glioblastoma stem cells neural stem cells tetraspanin true false true Angleški jezik Ni določen Neznano 2024-07-26 09:25:30 2024-07-26 09:25:30 2024-07-29 04:01:45 0000-00-00 00:00:00 2016 0 0 Nasl. z nasl. zaslona; Opis vira z dne 12. 11. 2015; str. 593-609 no. 1 Vol. 7 2016 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2016-01-01 577.2 1949-2553 10.18632/oncotarget.5477 3660623 RAZ_Podergajs_Neza_2016.pdf RAZ_Podergajs_Neza_2016.pdf 1 145664DB76F1F52D5F4ACA74C6D64202 06178bc21c998608a56478a838f5b9e12adf54c6ecbb1f064d92e383fc3a35bb 89ae1991-4b10-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=27570 https://doi.org/10.18632/oncotarget.5477 0 52983b9a-4b10-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=27569 Nacionalni inštitut za biologijo 0 0 0