scholarly journals Extracellular vesicles derived from glioblastoma promote proliferation and migration of neural progenitor cells via PI3K-Akt pathway

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Jiabin Pan ◽  
Shiyang Sheng ◽  
Ling Ye ◽  
Xiaonan Xu ◽  
Yizhao Ma ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Progenitor Cells ◽  
Cell Lines ◽  
Neural Progenitor Cells ◽  
Mtor Pathway ◽  
Akt Pathway ◽  
Glioblastoma Cell ◽  
And Migration ◽  
Glioblastoma Cell Lines ◽  
Proliferation And Migration

Abstract Background Glioblastomas are lethal brain tumors under the current combinatorial therapeutic strategy that includes surgery, chemo- and radio-therapies. Extensive changes in the tumor microenvironment is a key reason for resistance to chemo- or radio-therapy and frequent tumor recurrences. Understanding the tumor-nontumor cell interaction in TME is critical for developing new therapy. Glioblastomas are known to recruit normal cells in their environs to sustain growth and encroachment into other regions. Neural progenitor cells (NPCs) have been noted to migrate towards the site of glioblastomas, however, the detailed mechanisms underlying glioblastoma-mediated NPCs’ alteration remain unkown. Methods We collected EVs in the culture medium of three classic glioblastoma cell lines, U87 and A172 (male cell lines), and LN229 (female cell line). U87, A172, and LN229 were co-cultured with their corresponding EVs, respectively. Mouse NPCs (mNPCs) were co-cultured with glioblastoma-derived EVs. The proliferation and migration of tumor cells and mNPCs after EVs treatment were examined. Proteomic analysis and western blotting were utilized to identify the underlying mechanisms of glioblastoma-derived EVs-induced alterations in mNPCs. Results We first show that glioblastoma cell lines U87-, A172-, and LN229-derived EVs were essential for glioblastoma cell prolifeartion and migration. We then demonstrated that glioblastoma-derived EVs dramatically promoted NPC proliferation and migration. Mechanistic studies identify that glioblastoma-derived EVs achieve their functions via activating PI3K-Akt-mTOR pathway in mNPCs. Inhibiting PI3K-Akt pathway reversed the elevated prolfieration and migration of glioblastoma-derived EVs-treated mNPCs. Conclusion Our findings demonstrate that EVs play a key role in intercellular communication in tumor microenvironment. Inhibition of the tumorgenic EVs-mediated PI3K-Akt-mTOR pathway activation might be a novel strategy to shed light on glioblastoma therapy.

Extracellular Vesicles Derived from Glioblastoma Promote Proliferation and Migration of Neural Progenitor Cells via PI3K-Akt Pathway

2021 ◽  
Author(s):  
Jiabin Pan ◽  
Shiyang Sheng ◽  
Ling Ye ◽  
Yizhao Ma ◽  
Lisha Qiu ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Progenitor Cells ◽  
Cell Lines ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Mtor Pathway ◽  
Glioblastoma Cell ◽  
And Migration ◽  
Glioblastoma Cell Lines ◽  
Proliferation And Migration

Abstract BackgroundGlioblastomas are lethal brain tumors under the current combinatorial therapeutic strategy that includes surgery, chemo- and radio-therapies. Extensive changes in the tumor microenvironment is a key reason for resistance to chemo- or radio-therapy and frequent tumor recurrences. Understanding the tumor-nontumor cell interaction in TME is critical for developing new therapy. Glioblastomas are known to recruit normal cells in their environs to sustain growth and encroachment into other regions. Neural progenitor cells (NPCs) have been noted to migrate towards the site of glioblastomas, however, the detailed mechanisms underlying glioblastoma-mediated NPCs’ alteration remain unkown. MethodsWe utilized two classic glioblastoma cell lines, U87- and A172, and collected EVs in the culture medium of those two lines. Mouse NPCs (mNPCs) were co-cultured with U87- or A172-derived EVs. EVs-treated mNPCs’ prolifeartion and migration were examined. Proteomic analysis and western-blot were utilized to identify the underlying mechanisms of glioblastoma EVs-induced alterations in mNPCs.ResultsWe show that glioblastoma cell lines U87- and A172-derived EVs dramatically promoted NPCs proliferation and migration. Mechanistic studies identify that EVs achieve their functions via activating PI3K-Akt-mTOR pathway in recipient cells. Inhibiting PI3K-Akt reversed the elevated prolfieration and migration of glioblastoma EVs-treated mNPCs. ConclusionOur findings demonstrate that EVs play a key role in intercellular communication in tumor microenvironment. Inhibition of the tumorgenic EVs-mediated PI3K-Akt-mTOR pathway activation might be a novel strategy to shed light on glioblastoma therapy.

scholarly journals Quantifying cell line specific proliferation and migration rates in glioblastoma cells

2019 ◽  
Author(s):  
Emil Rosén ◽  
Philip Gerlee ◽  
Sven Nelander
Keyword(s):  
Cell Lines ◽  
Approximate Bayesian Computation ◽  
Patient Specific ◽  
Glioblastoma Cell ◽  
Migration Rates ◽  
Computation Algorithm ◽  
And Migration ◽  
Approximate Bayesian ◽  
Glioblastoma Cell Lines ◽  
Proliferation And Migration

AbstractWe have characterised the migration and proliferation rates of a large number of patient-derived glioblastoma cell lines using an individual-based model coupled to an Approximate Bayesian Computation algorithm. We found that the cell lines exhibited a negative correlation between the rate of migration and rate of division. This observation agrees with the Go or Grow hypothesis and highlights patient-specific differences in migration and proliferation.

scholarly journals The Chk1 inhibitor SAR-020106 sensitizes human glioblastoma cells to irradiation, to temozolomide, and to decitabine treatment

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Ina Patties ◽  
Sonja Kallendrusch ◽  
Lisa Böhme ◽  
Eva Kendzia ◽  
Henry Oppermann ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Progenitor Cells ◽  
Cell Lines ◽  
Multimodal Treatment ◽  
Neural Progenitor Cells ◽  
Glioblastoma Cell ◽  
Chk1 Inhibitor ◽  
Induction Of Apoptosis ◽  
Glioblastoma Cell Lines

Abstract Background Glioblastoma is the most common and aggressive brain tumour in adults with a median overall survival of only 14 months after standard therapy with radiation therapy (IR) and temozolomide (TMZ). In a novel multimodal treatment approach we combined the checkpoint kinase 1 (Chk1) inhibitor SAR-020106 (SAR), disrupting homologue recombination, with standard DNA damage inducers (IR, TMZ) and the epigenetic/cytotoxic drug decitabine (5-aza-2′-deoxycitidine, 5-aza-dC). Different in vitro glioblastoma models are monitored to evaluate if the impaired DNA damage repair may chemo/radiosensitize the tumour cells. Methods Human p53-mutated (p53-mut) and -wildtype (p53-wt) glioblastoma cell lines (p53-mut: LN405, T98G; p53-wt: A172, DBTRG) and primary glioblastoma cells (p53-mut: P0297; p53-wt: P0306) were treated with SAR combined with TMZ, 5-aza-dC, and/or IR and analysed for induction of apoptosis (AnnexinV and sub-G1 assay), cell cycle distribution (nuclear PI staining), DNA damage (alkaline comet or gH2A.X assay), proliferation inhibition (BrdU assay), reproductive survival (clonogenic assay), and potential tumour stem cells (nestinpos/GFAPneg fluorescence staining). Potential treatment-induced neurotoxicity was evaluated on nestin-positive neural progenitor cells in a murine entorhinal-hippocampal slice culture model. Results SAR showed radiosensitizing effects on the induction of apoptosis and on the reduction of long-term survival in p53-mut and p53-wt glioblastoma cell lines and primary cells. In p53-mut cells, this effect was accompanied by an abrogation of the IR-induced G2/M arrest and an enhancement of IR-induced DNA damage by SAR treatment. Also TMZ and 5-aza-dC acted radioadditively albeit to a lesser extent. The multimodal treatment achieved the most effective reduction of clonogenicity in all tested cell lines and did not affect the ratio of nestinpos/GFAPneg cells. No neurotoxic effects were detected when the number of nestin-positive neural progenitor cells remained unchanged after multimodal treatment. Conclusion The Chk1 inhibitor SAR-020106 is a potent sensitizer for DNA damage-induced cell death in glioblastoma therapy strongly reducing clonogenicity of tumour cells. Selectively enhanced p53-mut cell death may provide stronger responses in tumours defective of non-homologous end joining (NHEJ). Our results suggest that a multimodal therapy involving DNA damage inducers and DNA repair inhibitors might be an effective anti-tumour strategy with a low risk of neurotoxicity.

scholarly journals β-Elemene inhibits the proliferation and migration of human glioblastoma cell lines via suppressing ring finger protein 135

2020 ◽  
Vol 23 (1) ◽  
pp. 43-49
Author(s):  
M Alizada ◽  
J Li ◽  
H Aslami ◽  
D Yang ◽  
T Korchuganova ◽  
...  
Keyword(s):  
Cell Lines ◽  
Ring Finger ◽  
Glioblastoma Cell ◽  
Ring Finger Protein ◽  
Control Groups ◽  
Human Glioblastoma ◽  
Finger Protein ◽  
And Migration ◽  
Glioblastoma Cell Lines ◽  
Proliferation And Migration

Abstractβ-Elemene is commonly used as an anti-cancer agent in different types of cancers and its effects on glioblastoma have been studied through different pathways. However, its effect through ring finger protein 135 (RNF135, OMIM 611358) (RNF135), which is upregulated in glioblastomas, has not yet been explored. The current study is focused on the effects of β-elemene on human glioblastoma cell lines U251, U118, A172 and U87 through RNF13 5. A cell counting kit-8 assay and wound healing assay have been utilized to test the proliferation and migration of the cells. Western blot and quantitative real-time-polymerase chain reaction (qRT-PCR) were used to evaluate the level of expression of RNF135. A model of nude mice was used to explore progression of the tumor in vivo. It was observed that increasing treatment time or dose of β-elemene remarkably decreased viability of the cells. The cells that were treated with β-elemene had a much lower speed of moving toward the gap in comparison to untreated cell lines. β-Elemene-treated cells showed a much lower level of expression of RNF135 mRNA than control groups (p <0.05) and the levels of RNF135 protein were lower in the cells treated with β-elemene than in control groups (p <0.05). Moreover, tumor progression in subcutaneous xenograft nude mice was delayed with the injection of β-elemene. Altogether, our findings suggest that β-elemene inhibits proliferation, migration and tumorigenicity of human glioblastoma cells through suppressing RNF135.

scholarly journals P11.02 Hypothermia effect on glioblastoma cell viability, proliferation and migration

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii42-iii42
Author(s):  
C Fulbert ◽  
C Gaude ◽  
E Sulpice ◽  
S Chabardès ◽  
D Ratel
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Resection Margin ◽  
Moderate Hypothermia ◽  
Glioblastoma Cell ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Glioblastoma Cell Lines ◽  
Proliferation And Migration

Abstract BACKGROUND Glioblastoma is the most common and aggressive primary brain tumor in adults. In spite of intensive treatment, patients have a poor prognosis with a median survival of 14–16 months. After surgical resection followed by postoperative chemoradiation (combined temozolomide treatment and radiotherapy), tumor recurs in the resection margin for more than 90% of patients. This recurrence results from the activation of residual glioblastoma cells beyond the resection cavity by therapy-induced injuries. To handle this issue, we propose therapeutic hypothermia as an adjuvant treatment, in order to place the resection margin in a state of hibernation. In fact, hypothermia was introduced as a promising therapeutic approach in various medical applications like cardiac arrest and pharmaco-resistant epilepsy. Only a few in vitro studies explored the effects of hypothermia on cancer cells and showed promising results. The aim of our work is to investigate the effects of hypothermia on glioblastoma cell proliferation and migration, two key cellular processes involved in cancer progression. MATERIAL AND METHODS We performed in vitro experiments on glioblastoma cell lines with different p53 status and various growth rates. For exploring the therapeutic potential of both mild and moderate hypothermia, we studied their impact on cell viability, proliferation and migration. We also performed cell cycle analysis by quantitation of DNA content using flow cytometry. RESULTS Results were similar for all glioblastoma cell lines, and demonstrated that cells were extremely sensitive to hypothermia. We showed that both mild and moderate hypothermia induced significant changes on glioblastoma cell lines behavior with a strong inhibition of cell proliferation and migration. Moderate hypothermia also affected glioblastoma cell viability and modified their distribution into the cell cycle phases. CONCLUSION Our results were comparable in all glioblastoma cell lines tested, demonstrating a consistent and universal effect of hypothermia. We showed that hypothermia significantly inhibits cell proliferation and migration, which are key processes involved in tumor growth. Proliferation arrest could be explained by the accumulation of cells in the G2/M phase of the cell cycle. Together, these results support hypothermia as a promising adjuvant therapy for glioblastoma patients. Indeed, combined with current treatments, moderate hypothermia applied at the resection margin could prevent tumor recurrence after surgical resection. There is a crucial need to propose innovative glioblastoma treatments, and hypothermia appears as a promising therapeutic way. SUPPORT This work received financial support through grants from the Groupement des Entreprises Françaises de Lutte contre le Cancer (GEFLUC Grenoble - Dauphiné - Savoie) and the Fonds de dotation Clinatec.

Arctigenin upregulates apoptosis through the AKT/MTOR pathway, inhibiting the proliferation of glioma

2019 ◽  
Author(s):  
jiang yongan ◽  
Liu Jia yu ◽  
Hong Wangwang ◽  
Fei Xiaowei ◽  
Liu ru'en
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Glioma Cells ◽  
Mtor Pathway ◽  
Migration And Invasion ◽  
Glioblastoma Cell ◽  
Caspase 9 ◽  
Arctium Lappa ◽  
Dose Dependent ◽  
Glioblastoma Cell Lines

Abstract Arctigenin (ARG) is a natural lignan compound extracted from arctium lappa and has displayed anticancer functions and effective treatments in a variety of cancers.Studies had shown that Arctigenin(ARG) inhibits tumors through the AKT/MTOR pathway and mediates autophagy.However,the role in glioma cellshave not still fully understood.This study was designed to investigate whether Arctigenin(ARG) can mediateAKT/mTOR pathway in glioma to regulate autophagy,and affected glioma cells growth and survival.We found that the dose-dependent downregulation of Arctigenin(ARG),reducing cell proliferation,migration and invasion in two human glioblastoma cell lines (U87, T98G),These phenomena were reversed after the administration of the AKT agonist (SC79). Arctigenin(ARG) also affected other autophagy markers such as p62, LC3B.In addition, the apoptotic molecules cleaved-PARP,caspase-9, and cleaved-caspase3 were also dose-dependently altered.

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