Effect of Selection Pressure with Temozolomide on Cripto-1 Expression in Glioblastoma In Vitro Models
Author
Yener, Cansu
Term
4. term
Publication year
2018
Submitted on
2018-05-30
Pages
46
Abstract
Baggrund: Glioblastoma multiforme (GBM) er en meget aggressiv grad IV-hjernetumor med en median overlevelse på 12–15 måneder. Standardbehandling (operation, kemo- og stråleterapi) forlænger livet lidt, men helbreder sjældent, og tumoren vokser ofte ud igen. En mulig forklaring er en lille bestand af glioblastom-initiationsceller (GIC’er), der kan vandre, ligner stamceller og tåler almindelige behandlinger. Proteinet Cripto-1 (CR-1) er sat i forbindelse med kræft og foreslået som markør for GIC’er, og kunne derfor være et muligt behandlingsmål. Formål og metode: Vi undersøgte, hvordan to behandlingsrunder med kemolægemidlet temozolomid (TMZ) påvirker laboratoriedyrkede GBM-cellelinjer (U87, T78 og T87), og om ændringer i CR-1 hænger sammen med cellernes evne til selvfornyelse (dvs. at danne nye celler over tid). DMSO fungerede som opløsningsmiddelkontrol. Vi målte cellers overlevelse og vækst (viabilitet og proliferation) samt selvfornyelse og kvantificerede CR-1-niveauer med qPCR og flowcytometri. Resultater: U87-celler var følsomme over for TMZ med lavere viabilitet, langsommere vækst og nedsat selvfornyelse; CR-1 faldt efter behandling. T78-celler faldt i funktioner efter første runde, men viste igen fremgang efter anden runde. T87-celler lignede kontrolgruppen (DMSO), og CR-1 steg efter anden TMZ-runde. DMSO alene sænkede proliferation i alle tre cellelinjer. Konklusion: Cellelinjerne reagerede forskelligt på gentagen TMZ-behandling, hvilket kan hænge sammen med deres genetiske forskelle. I denne undersøgelse fungerede CR-1 ikke som en pålidelig markør for GIC-egenskaberne. Der er behov for mere forskning i, hvordan TMZ påvirker GBM in vitro, og hvordan GIC-populationen ændres under behandlingspres.
Background: Glioblastoma multiforme (GBM) is a highly aggressive grade IV brain cancer with a median survival of 12–15 months. Standard treatments (surgery, chemo- and radiotherapy) offer limited life extension and rarely cure the disease, and tumors often regrow. One explanation is a small subset of glioblastoma-initiating cells (GICs) that can migrate, show stem cell–like traits, and resist conventional therapies. The protein Cripto-1 (CR-1) has been linked to cancer and proposed as a marker of GICs, making it a potential therapeutic target. Aim and methods: We examined how two cycles of the chemotherapy drug temozolomide (TMZ) affect GBM cell lines grown in the lab (U87, T78, T87), and whether changes in CR-1 relate to cells’ self-renewal ability (their capacity to generate new cells over time). Dimethyl sulfoxide (DMSO) served as the vehicle control. We assessed cell survival and growth (viability and proliferation) and self-renewal, and measured CR-1 levels using qPCR and flow cytometry. Results: U87 cells were sensitive to TMZ, showing reduced viability, slower growth, and lower self-renewal; CR-1 decreased after treatment. T78 cells declined after the first cycle but rebounded after the second. T87 cells resembled the DMSO control, and CR-1 increased after the second TMZ cycle. DMSO alone reduced proliferation in all three cell lines. Conclusion: The cell lines responded differently to repeated TMZ, likely reflecting genetic differences. In this study, CR-1 did not serve as a reliable marker of GIC features. Further work is needed to clarify how TMZ affects GBM in vitro and how the GIC population changes under treatment pressure.
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