Effects of Single or Combined Treatments with Radiation and Chemotherapy on Survival and Danger Signals Expression in Glioblastoma Cell Lines

Pasi, Francesca; Paolini, Alessandro; Nano, Rosanna; Liberto, Riccardo Di; Capelli, Enrica

doi:10.1155/2014/453497

Cited by 29 publications

(25 citation statements)

References 25 publications

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“…The intracellular Hsp70 levels remain unaltered in sham treated tumor cells, whilst during irradiation with a sublethal dose of 2 Gy and directly after irradiation with lethal doses [28] results in a considerable increase in the Hsp70 synthesis [2,10,16,29]. In line with our assumption that synthesis and expression of Hsp70 is dependent on doseand time-dependent factors it can be assumed that cytoprotective repair mechanisms that depend on the anti-apoptotic molecular chaperone Hsp70 are also related to the applied stress.…”

Section: Discussionsupporting

confidence: 72%

“…Although the major goal of irradiation is the reduction in viable tumor mass to achieve local tumor control and a decreased dissemination, also immunostimulatory effects have been assigned to ionizing radiation [2]. However, it remains to be elucidated which dose and radiation regimen is optimal to induce abscopal anti-tumor immune effects.…”

Section: Introductionmentioning

confidence: 99%

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

Fellinger¹,

Stangl²,

Hernández³

et al. 2019

Preprint

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The major stress-inducible Hsp70 (HSPA1A) is overexpressed in highly aggressive tumor cells including glioblastoma multiforme and presented on their plasma membrane. Ionizing irradiation increases cytosolic and membrane-bound Hsp70 (mHsp70) on tumor cells. Depending on its intracellular or membrane localization, Hsp70 either promotes tumor growth or serves as a target for the innate immune system. To define the optimal window for a therapy with Hsp70-tageting NK cells the kinetics of the mHsp70 density on the plasma membrane of human glioma cells (U87) has been studied after radiotherapy by multiparameter flow cytometry. Cell cycle dependent alterations in the mHsp70 expression were excluded by seeding different cell numbers on day 0. Low dose irradiation (2 Gy) results in a slow upregulation of the mHsp70 density in U87 cells which peaks on day 4 and starts to decline from day 7 onwards. In contrast, higher radiation doses (4 Gy, 6 Gy) resulted in a faster upregulation of mHsp70 expression on days 2 and 1, respectively, followed by a decline from day 5 onwards. Functionally, elevated mHsp70 densities correlate with an improved 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.

show abstract

Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

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

Fellinger¹,

Stangl²,

Hernández³

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Ionizing radiation elicits its cytotoxic activity against tumor cells by causing DNA single-and double-strand breaks, predominantly mediated and fixed by reactive oxygen species (ROS). Although the major goal of irradiation is to achieve local tumor control and a decreased dissemination by reducing the viable tumor mass, also immunostimulatory effects have been assigned to ionizing radiation [1,2]. However, it remains to be elucidated which dose and radiation regimen is optimal to induce anti-tumor immune effects.…”

Section: Introductionmentioning

confidence: 99%

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

Fellinger

Stangl

Schnelzer

et al. 2020

Cells

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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.

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“…4 Previous studies have demonstrated that irradiation and chemotherapy can enhance the effect of immunotherapies against GBM via various mechanisms. 8 For instance, irradiation and chemotherapy induce apoptosis in highly proliferating cells, making them more available for phagocytosis by APCs (e.g., macrophages, microglia, dendritic cells), which then present tumor Ags to adaptive immune cells. This effect further activates the antitumor immune response.…”

Section: Introductionmentioning

confidence: 99%

Irradiation or temozolomide chemotherapy enhances anti-CD47 treatment of glioblastoma

et al. 2019

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Irradiation and temozolomide (TMZ) chemotherapy are the current standard treatments for glioblastoma multiforme (GBM), but they are associated with toxicity and limited efficacy. Recently, these standard therapies have been used to enhance immunotherapy against GBM. Immunotherapy using the anti-CD47 (immune checkpoint inhibitor) treatment has shown promise in treating multiple tumor types, including GBM. The goal of this current work was to test whether irradiation or TMZ chemotherapy could enhance anti-CD47 treatment against GBM. Our results showed that irradiation and TMZ each significantly enhanced anti-CD47-mediated phagocytosis of GBM cells in vitro. Furthermore, mice engrafted with human GBM that received anti-CD47 combined with focal irradiation or TMZ treatment showed a significant increase in the survival rate compared to those that received a single treatment. The tumor growth in mice that received both anti-CD47 and irradiation was significantly less than that of groups that received either anti-CD47 or focal irradiation. The results from this study may support future use of anti-CD47 treatment in combination with irradiation or chemotherapy to enhance the therapeutic efficacy of GBM treatment.

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Effects of Single or Combined Treatments with Radiation and Chemotherapy on Survival and Danger Signals Expression in Glioblastoma Cell Lines

Cited by 29 publications

References 25 publications

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

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

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

Irradiation or temozolomide chemotherapy enhances anti-CD47 treatment of glioblastoma

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