20.500.12556/DiRROS-19647 Cysteine cathepsins B, X and K expression in peri-arteriolar glioblastoma stem cell niches Glioblastoma (GBM) is the most lethal brain tumor also due to malignant and therapy-resistant GBM stem cells (GSCs) that are localized in protecting hypoxic GSC niches. Some members of the cysteine cathepsin family of proteases have been found to be upregulated in GBM. Cathepsin K gene expression is highly elevated in GBM tissue versus normal brain and it has been suggested to regulate GSC migration out of the niches. Here, we investigated the cellular distribution of cathepsins B, X and K in GBM tissue and whether these cathepsins are co-localized in GSC niches. Therefore, we determined expression of these cathepsins in serial paraffin sections of 14 human GBM samples and serial cryostat sections of two samples using immunohistochemistry and metabolic mapping of cathepsin activity using selective fluorogenic substrates. We detected cathepsins B, X and K in peri-arteriolar GSC niches in 9 out of 16 GBM samples, which were defined by co-expression of the GSC marker CD133, the niche marker stromal-derived factor-1α (SDF-1α) and smooth muscle actin as a marker for arterioles. The expression of cathepsin B and X was detected in stromal cells and cancer cells throughout the GBM sections, whereas cathepsin K expression was more restricted to arteriole-rich regions in the GBM sections. Metabolic mapping showed that cathepsin B, but not cathepsin K is active in GSC niches. On the basis of these findings, it is concluded that cathepsins B, X and K have distinct functions in GBM and that cathepsin K is the most likely GSC niche-related cathepsin of the three cathepsins investigated. cysteine cathepsins glioblastoma stem cells niches stroma proteolytic activity true false true Angleški jezik Ni določen Neznano 2024-07-23 03:54:45 2024-07-24 13:11:57 2024-07-25 04:14:51 0000-00-00 00:00:00 2018 0 0 str. 481-497 no. 5 Vol. 49 2018 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2018-07-25 577.2 1567-2379 10.1007/s10735-018-9787-y 4768847 RAZ_Breznik_Barbara_2018.pdf RAZ_Breznik_Barbara_2018.pdf 1 FB503791F1F20DF0F1035FC963C0B1A8 8c541db18991c4b8037aae6d21eae6a070b62654453f94a766c0e43e01025818 d49e9ccd-499c-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=27316 https://doi.org/10.1007/s10735-018-9787-y 0 e4baefb5-499c-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=27317 Nacionalni inštitut za biologijo 0 0 0