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Vpliv mezenhimskih matičnih celic na proliferacijo in invazivnost celic glioblastoma v možganih zarodkov cebric (Danio rerio)
ID Božič, Lara (Author), ID Vittori, Miloš (Mentor) More about this mentor... This link opens in a new window, ID Breznik, Barbara (Co-mentor)

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Abstract
Možganski tumor glioblastom (GB) je najpogostejši in najagresivnejši primarni tumor osrednjega živčnega sistema pri odraslih. Zdravljenje je zaradi odpornosti tumorja na kemo- in radioterapijo ter nepopolne kirurške odstranitve neuspešno. K temu prispeva heterogenost GB. Rakave celice so v tumorju obdane s kompleksnim tumorskim mikrookoljem. Medcelična komunikacija v mikrookolju prispeva k razvoju tumorja. Glioblastomske matične celice (GMC) so odporne na terapijo in zaščitene v posebnem mikrookolju – niši. V niši sobivajo z nerakavimi stromalnimi celicami, kot so mezenhimske matične celice (MMC). Preučevali smo vpliv MMC na rast in invazijo GMC v možganih zarodkov cebric (Danio rerio). V možgane zarodkov smo vnesli GMC ter mešanice GMC in MMC, kar nam je omogočilo primerjavo tumorjev. S programom ImageJ smo kvantificirali relativno spremembo površine in dolžine tumorjev monokultur in sokultur celic v možganih in vivo. Razvili in optimizirali smo metodo priprave tkivih rezin možganov z vnesenimi označenimi humanimi celicami za imunohistokemijsko barvanje. Uporabili smo označevalce matičnosti in invazije GMC, s katerimi smo analizirali medsebojni vpliv celic. Ugotovili smo, da GMC in MMC v možganih cebric tvorijo mešane tumorje. Pokazali smo, da prisotnost MMC ne spremeni proliferacije, ne sproži diferenciacije in ne spremeni invazije GMC v možganih cebric. Prisotnost GMC je povečala rast in invazijo MMC.

Language:Slovenian
Keywords:glioblastom, glioblastomske matične celice, mezenhimske matične celice, cebrice, rast celic, invazija, parafinske rezine, imunohistokemijsko barvanje
Work type:Master's thesis/paper (mb22)
Typology:2.09 - Master's Thesis
Organization:BF - Biotechnical Faculty
Year:2021
Publisher:[L. Božič]
Place:Ljubljana
UDC:602.9:591.81:601.4:577.21(043.2)
COBISS.SI-ID:72131331 This link opens in a new window
Publication date in RUL:18.07.2021
Views:423
Downloads:58
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Secondary language

Language:English
Title:Impact of mesenchymal stem cells on the proliferation and invasion of glioblastoma cells in the zebrafish (Danio rerio) embryonic brain
Abstract:
Glioblastoma (GB) is the most common and most aggressive brain tumor of primary central nervous system in humans. Treatment is unsuccessful due to the tumor's resistance to chemotherapy, radiotherapy and incomplete surgical removal. GB displays extensive cellular heterogeneity which represents a major obstacle for effective treatment. Cancer cells in a tumor are surrounded by a complex tumor microenvironment (TMO). Intercellular interactions within the TMO drive tumor progression. Glioblastoma stem cells (GMC) are resistant to therapy and protected in a special microenvironment - a niche. They coexist in the niche with non-cancerous stromal cells such as mesenchymal stem cells (MMC). We studied the impact of MMC on the proliferation and invasion of GMC in the zebrafish embryonic brain. We injected GMC and mixtures of GMC and MMC into the embryonic brain, which allowed us to compare tumors. The program ImageJ was used to quantify the relative difference of area and length of monoculture and coculture tumors in the brain in vivo. We developed and optimized a method of preparing zebrafish brain tissue sections, with injected labeled human cells, for immunohistochemistry. We used stem cell markers and markers of cancer cell invasion for interaction analysis. We found that GMC and MMC form mixed tumors in the zebrafish brain. We have shown that the presence of MMC does not alter proliferation, does not trigger differentiation, and does not alter invasion of GMC in the zebrafish brain. The presence of GMC increased the growth and invasion of MMC.

Keywords:glioblastoma, glioblastoma stem cells, mesenchymal stem cells, zebrafish, invasion, cell growth, imunohistochemistry, paraffin sections

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