Interakcije med celicami glioblastoma in mezenhimskimi matičnimi celicami in vitro ter v možganih cebric

Šijanec, Nika (author), Vittori, Miloš (mentor), Breznik, Barbara (comentor)

Glioblastom (GB) je najpogostejši in najagresivnejši možganski tumor pri človeku. Glioblastomske matične celice (GMC) so odgovorne za rezistenco na radio- in kemoterapijo, ohranjanje in širjenje GB ter njegovo ponovitev. V tumorskem mikrookolju so prisotne tudi mezenhimske matične celice (MMC), ki z interakcijami s celicami GB pospešijo razvoj GB. Zaenkrat še ni znano, kako MMC vplivajo na rast ter invazijo GMC. Vpliv celičnih interakcij med GMC in MMC na rast in invazijo celic GB smo določali v 3D modelu sferoidov in vitro ter v možganih zarodkov rib cebric (Danio rerio). Pokazali smo, da MMC vplivajo na morfologijo GMC v sferoidih sokultur. Z uporabo konfokalne mikroskopije smo razlike v morfologiji med GMC v monokulturi in sokulturi z MMC potrdili tudi v modelu in vivo. Naši rezultati kažejo, da prisotnost MMC poveča rast GMC v modelih tumorja in vitro ter in vivo. MMC so bile v primerjavi z GMC bolj invazivne, v sokulturi pa so GMC zmanjšale invazijo MMC in vitro. MMC na invazijo GMC in vitro ter in vivo niso imeli učinka. Nasprotno smo v modelu in vivo pokazali večjo invazijo GMC v primerjavi z injiciranimi MMC. Razlog za razlike v invaziji pri dveh različnih uporabljenih modelih je v mikrookolju, ki je v možganih cebric kompleksnejše. Pokazali smo, da so MMC v tumorskem mikrookolju pomembne, saj pospešijo rast GMC.

• Language: Slovenian
• Keywords: glioblastom, glioblastomske matične celice, mezenhimske matične celice, cebrice, rast celic, invazija
• Work type: Master's thesis/paper
• Organization: BF - Biotechnical Faculty
• Year: 2020
• PID: 20.500.12556/RUL-120565
• COBISS.SI-ID: 34552835
• Publication date in RUL: 23.09.2020

ŠIJANEC, Nika, 2020, Interakcije med celicami glioblastoma in mezenhimskimi matičnimi celicami in vitro ter v možganih cebric [online]. Master’s thesis. [Accessed 2 April 2025]. Retrieved from: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=eng&id=120565

Secondary language

• Language: English
• Title: Interactions between glioblastoma cells and mesenchymal stem cells in vitro and in the zebrafish brain

Abstract

Glioblastoma (GB) is the most common and most aggressive brain tumour in humans. Glioblastoma stem cells (GMC) are responsible for resistance to radiotherapy and chemotherapy, the maintenance and spread of the tumour, and its recurrence. Mesenchymal stem cells (MMC) are also present in the tumour microenvironment, which, through interactions with glioblastoma cells, promote GB development and increase the self-renewal capacity of GMC and their invasion. It has not been studied so far how MMC affect GMC growth and invasion. We determined the influence of cellular interactions between GMC and MMC on the growth and invasion of glioblastoma cells in a 3D model of spheroids in vitro and in the brains of zebrafish embryos (Danio rerio). We showed that MMC affected the morphology of GMC in the spheroids of co-culture. Using confocal microscopy, we also showed differences in morphology between GMC in monoculture and co-culture with MMC in vivo. We demonstrated that the presence of MMC increased GMC growth in in vitro and in vivo tumour models. MMCs were more invasive than GMCs, but in co-culture GMCs reduced MMC invasion in vitro. In contrast, GMC invasion was significantly higher in the in vivo model compared to injected MMCs. The reason for the differences in invasion in different models used is in the microenvironment, which is more complex in the brains of zebrafish. We showed that MMCs are important in the tumour microenvironment as they promote GMC growth.

• Keywords: glioblastoma, glioblastoma stem cells, mesenchymal stem cells, zebrafish, invasion