Quantifying cell line specific proliferation and migration rates in glioblastoma cells

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.

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

10.21203/rs.3.rs-153837/v1 ◽

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.

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

Cell Communication and Signaling ◽

10.1186/s12964-021-00760-9 ◽

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.

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

Balkan Journal of Medical Genetics ◽

10.2478/bjmg-2020-0002 ◽

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.

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

Neuro-Oncology ◽

10.1093/neuonc/noz126.148 ◽

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.

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In Vitro/In Silico Study on the Role of Doubling Time Heterogeneity among Primary Glioblastoma Cell Lines

BioMed Research International ◽

10.1155/2017/8569328 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 11

Author(s):

M.-E. Oraiopoulou ◽

E. Tzamali ◽

G. Tzedakis ◽

A. Vakis ◽

J. Papamatheakis ◽

...

Keyword(s):

Cell Lines ◽

In Silico ◽

Intratumoral Heterogeneity ◽

Patient Specific ◽

Cell Physiology ◽

Glioblastoma Cell ◽

Glioblastoma Cells ◽

Primary Glioblastoma ◽

Glioblastoma Cell Lines

The application of accurate cancer predictive algorithms validated with experimental data is a field concerning both basic researchers and clinicians, especially regarding a highly aggressive form of cancer, such as Glioblastoma. In an aim to enhance prediction accuracy in realistic patient-specific environments, accounting for both inter- and intratumoral heterogeneity, we use patient-derived Glioblastoma cells from different patients. We focus on cell proliferation using in vitro experiments to estimate cell doubling times and sizes for established primary Glioblastoma cell lines. A preclinically driven mathematical model parametrization is accomplished by taking into account the experimental measurements. As a control cell line we use the well-studied U87MG cells. Both in vitro and in silico results presented support that the variance between tumor staging can be attributed to the differential proliferative capacity of the different Glioblastoma cells. More specifically, the intratumoral heterogeneity together with the overall proliferation reflected in both the proliferation rate and the mechanical cell contact inhibition can predict the in vitro evolution of different Glioblastoma cell lines growing under the same conditions. Undoubtedly, additional imaging techniques capable of providing spatial information of tumor cell physiology and microenvironment will enhance our understanding regarding Glioblastoma nature and verify and further improve our predictability.

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