• search hit 8 of 1542
Back to Result List

Migration pattern, actin cytoskeleton organization and response to PI3K-, mTOR-, and Hsp90-inhibition of glioblastoma cells with different invasive capacities

Please always quote using this URN: urn:nbn:de:bvb:20-opus-170719
  • High invasiveness and resistance to chemo- and radiotherapy of glioblastoma multiforme (GBM) make it the most lethal brain tumor. Therefore, new treatment strategies for preventing migration and invasion of GBM cells are needed. Using two different migration assays, Western blotting, conventional and super-resolution (dSTORM) fluorescence microscopy we examine the effects of the dual PI3K/mTOR-inhibitor PI-103 alone and in combination with the Hsp90 inhibitor NVP-AUY922 and/or irradiation on the migration, expression of marker proteins, focalHigh invasiveness and resistance to chemo- and radiotherapy of glioblastoma multiforme (GBM) make it the most lethal brain tumor. Therefore, new treatment strategies for preventing migration and invasion of GBM cells are needed. Using two different migration assays, Western blotting, conventional and super-resolution (dSTORM) fluorescence microscopy we examine the effects of the dual PI3K/mTOR-inhibitor PI-103 alone and in combination with the Hsp90 inhibitor NVP-AUY922 and/or irradiation on the migration, expression of marker proteins, focal adhesions and F-actin cytoskeleton in two GBM cell lines (DK-MG and SNB19) markedly differing in their invasive capacity. Both lines were found to be strikingly different in morphology and migration behavior. The less invasive DK-MG cells maintained a polarized morphology and migrated in a directionally persistent manner, whereas the highly invasive SNB19 cells showed a multipolar morphology and migrated randomly. Interestingly, a single dose of 2 Gy accelerated wound closure in both cell lines without affecting their migration measured by single-cell tracking. PI-103 inhibited migration of DK-MG (p53 wt, PTEN wt) but not of SNB19 (p53 mut, PTEN mut) cells probably due to aberrant reactivation of the PI3K pathway in SNB19 cells treated with PI-103. In contrast, NVP-AUY922 exerted strong anti-migratory effects in both cell lines. Inhibition of cell migration was associated with massive morphological changes and reorganization of the actin cytoskeleton. Our results showed a cell line-specific response to PI3K/mTOR inhibition in terms of GBM cell motility. We conclude that anti-migratory agents warrant further preclinical investigation as potential therapeutics for treatment of GBM.show moreshow less

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar Statistics
Metadaten
Author: Simon Memmel, Dmitri Sisario, Caren Zöller, Vanessa Fiedler, Astrid Katzer, Robin Heiden, Nicholas Becker, Lorenz Eing, Fábio L.R. Ferreira, Heiko Zimmermann, Markus Sauer, Michael Flentje, Vladimir L. Sukhorukov, Cholpon S. Djuzenova
URN:urn:nbn:de:bvb:20-opus-170719
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Strahlentherapie
Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Parent Title (English):Oncotarget
Year of Completion:2017
Volume:8
Issue:28
Pagenumber:45298-45310
Source:Oncotarget 2017, Vol. 8, No. 28, 45298-45310. DOI: 10.18632/oncotarget.16847
DOI:https://doi.org/10.18632/oncotarget.16847
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=28424411
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:chemotherapy; glioblastoma multiforme; migration; treatment
Release Date:2019/10/04
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung