Next Article in Journal
Targeted PARP Inhibition Combined with FGFR1 Blockade is Synthetically Lethal to Malignant Cells in Patients with Pancreatic Cancer
Previous Article in Journal
Exploring the Relevance of Senotherapeutics for the Current SARS-CoV-2 Emergency and Similar Future Global Health Threats
Previous Article in Special Issue
Cross Interaction between M2 Muscarinic Receptor and Notch1/EGFR Pathway in Human Glioblastoma Cancer Stem Cells: Effects on Cell Cycle Progression and Survival
Open AccessArticle

Time- and Dose-Dependent Effects of Ionizing Irradiation on the Membrane Expression of Hsp70 on Glioma Cells

1
Radiation Immuno-Oncology Group, Center for Translational Cancer Research (TranslaTUM), School of medicine, Technical University of Munich (TUM), 81675 Munich, Germany
2
Institute of the Russian Academy of Sciences (RAS), 194064 St. Petersburg, Russia
3
Department of Biotechnology, Pavlov First Saint Petersburg State Medical University, 197022 St. Petersburg, Russia
4
Institute of Medical Informatics, Statistics and Epidemiology, Technical University of Munich (TUM), 81675 Munich, Germany
5
Department of Radiation Oncology, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany
*
Author to whom correspondence should be addressed.
Cells 2020, 9(4), 912; https://doi.org/10.3390/cells9040912
Received: 24 March 2020 / Revised: 6 April 2020 / Accepted: 7 April 2020 / Published: 8 April 2020
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Cancers: Glioblastoma)
The major stress-inducible protein Hsp70 (HSPA1A) is overexpressed in the cytosol of many highly aggressive tumor cells including glioblastoma multiforme and presented on their plasma membrane. Depending on its intracellular or membrane localization, Hsp70 either promotes tumor growth or serves as a target for natural killer (NK) cells. The kinetics of the membrane Hsp70 (mHsp70) density on human glioma cells (U87) was studied after different irradiation doses to define the optimal therapeutic window for Hsp70-targeting NK cells. To maintain the cells in the exponential growth phase during a cultivation period of 7 days, different initial cell counts were seeded. Although cytosolic Hsp70 levels remained unchanged on days 4 and 7 after a sublethal irradiation with 2, 4 and 6 Gy, a dose of 2 Gy resulted in an upregulated mHsp70 density in U87 cells which peaked on day 4 and started to decline on day 7. Higher radiation doses (4 Gy, 6 Gy) resulted in an earlier and more rapid onset of the mHsp70 expression on days 2 and 1, respectively, followed by a decline on day 5. Membrane Hsp70 levels were higher on cells in G2/M than in G1; however, an irradiation-induced cell cycle arrest on days 4 and 7 was not associated with an increase in the mHsp70 density. Extracellular Hsp70 concentrations in the supernatant of irradiated cells were significantly higher than sham (0 Gy) irradiated cells on days 4 and 7, but not on day 1. Functionally, elevated mHsp70 densities were associated with a significantly better lysis by Hsp70-targeting NK cells. In summary, the kinetics of changes in the mHsp70 density upon irradiation on tumor cells is time- and dose-dependent. View Full-Text
Keywords: radiotherapy; glioblastoma; membrane Hsp70; dose- and time-kinetics; NK cell-based therapy radiotherapy; glioblastoma; membrane Hsp70; dose- and time-kinetics; NK cell-based therapy
Show Figures

Graphical abstract

MDPI and ACS Style

Fellinger, H.; Stangl, S.; Hernandez Schnelzer, A.; Schwab, M.; Di Genio, T.; Pieper, M.; Werner, C.; Shevtsov, M.; Haller, B.; Multhoff, G. Time- and Dose-Dependent Effects of Ionizing Irradiation on the Membrane Expression of Hsp70 on Glioma Cells. Cells 2020, 9, 912.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop