Vloga cisteinske peptidaze katepsina X v glioblastomskih matičnih celicah

Bionda, Gregor (author), Pišlar, Anja (mentor)

Glioblastomske matične celice (GMC) so majhna populacija slabo diferenciranih celic, prisotna v multiformnem glioblastomu (GBM), eni izmed oblik možganskega tumorja. Imajo samoobnovitveni potencial in so se sposobne diferencirati v različne vrste tumorskih celic. Odporne so na vse oblike zdravljenja in tako vedno ostane majhen delež teh celic, ki so odgovorne za ponovno rast tumorja. Zato bi bila za uspešno terapijo glioblastoma potrebna odstranitev prav vseh GMC. K invazivnosti in celični migraciji glioblastomskih celic prispeva izražanje in delovanje cisteinske karboksi peptidaze katepsina X, ki ima pomembno vlogo pri tumorski progresiji. V magistrski nalogi smo na glioblastomski celični liniji U87 želeli ovrednotiti vlogo katepsina X v celicah, podobnim glioblastomskim matičnim celicam (GSCs). Celice U87 so sposobne tvorbe tridimenzionalnih celičnih skupkov, t.i. sferoidov, s katerimi se zaščitijo pred stimulusi iz okolja. Naši rezultati so pokazali, da s stimulacijo celic U87 dosežemo ekspanzijo celic GSCs. Hkrati smo v teh celicah pokazali povečano izražanje katepsina X, ki predstavlja možno novo tarčo pri obravnavanju zdravljenja GBM. V zadnjem delu magistrske naloge smo opazovali ekspanzijo celic GSCs ob prisotnosti specifičnega zaviralca katepsina X. Pri tem smo pokazali, da zaviranje katepsina X pomembno vpliva na ekspanzijo celic GSCs. Iz zbranih rezultatov lahko sklepamo o pomembnosti katepsina X v GMC, hkrati pa vidimo da bi uravnavanje proteaze v teh celicah lahko vodilo v nove možnosti zdravljenja GBM.

• Language: Slovenian
• Keywords: multiformni glioblastom, glioblastomske matične celice, katepsin X, ireverzibilni zaviralec
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2019
• PID: 20.500.12556/RUL-106823
• Publication date in RUL: 18.03.2019

Secondary language

• Language: English
• Title: The role of cysteine peptidase cathepsin X in glioblastoma stem cells

Abstract

Glioblastoma multiforme (GBM) is the most aggressive form of brain tumour and contains a population of non-differentiated cells called glioblastoma stem cells (GSC). These cells are capable of self-renovation, they have unlimited capability to divide and the capacity to differentiate themselves into other tumour cells as well. It has also been proven that this population of cells can regenerate tumour mass after it has been removed. This leads to the presumption that they can become an important target in GBM treatment. The goal of the treatment is to eradicate every GSC, but because of their resistance to chemo- and radiotherapy, this issue remains unresolved. In this master thesis research, we were investigating the role of cysteine peptidase cathepsin X in glioblastoma stem-like cells (GSCs). Cathepsin X impacts migration and invasion of GSCs and therefore plays an important role in tumour progression. We used glioblastoma cell line U87, which can form cell clusters, so called spheroids, which protect them from external stimuli. Our results indicate that the stimulation of U87 cells increases the expansion of GSCs. Moreover, we demonstrated overexpression and localization of cathepsin X in GSCs. We confirmed that cathepsin X has a significant role in GSCs and could be an important target in the GBM treatment. To sum up the investigation we observed the expansion of GSCs by stimulating U87 cells with the presence of a specific inhibitor of cathepsin X. We showed that by the selective cathepsin X inhibition, there was observed a significant impact in the expansion of GSCs. In this context we believe that cathepsin X plays an important role in GBM tumour progression.

• Keywords: glioblastoma multiforme, glioblastoma stem cells, cathepsin X, irreversible inhibitor