The inhibiting effect of neural stem cells on proliferation and invasion of glioma cells

Exploitation of the potential ability of human olfactory bulb (hOB) cells to carry, release, and deliver an effective, targeted anticancer therapy within the central nervous system (CNS) milieu remains elusive. Previous studies have demonstrated the marked ability of several types of stem cells (such as mesenchymal stem cells (MSCs) to carry and release different anti-cancer agents such as paclitaxel (PTX). Herein we investigate the ability of human olfactory bulb neural stem cells (Hu-OBNSCs) to carry and release paclitaxel, producing effective cytotoxic effects against cancer cells. We isolated Hu-OBNSCs from the hOB, uploaded them with PTX, and studied their potential cytotoxic effects against cancer cells in vitro. Interestingly, the Hu-OBNSCs displayed a five-fold increase in their resistance to the cytotoxicity of PTX, and the PTX-uploaded Hu-OBNSCs were able to inhibit proliferation and invasion, and to trigger marked cytotoxic effects on glioblastoma multiforme (GBM) cancer cells, and Human Caucasian fetal pancreatic adenocarcinoma 1 (CFPAC-1) in vitro. Despite their ability to resist the cytotoxic activity of PTX, the mechanism by which Hu-OBNSCs acquire resistance to PTX is not yet explained. Collectively our data indicate the ability of the Hu-OBNSCs to resist PTX, and to trigger effective cytotoxic effects against GBM cancer cells and CFPAC-1. This indicates their potential to be used as a carrier/vehicle for targeted anti-cancer therapy within the CNS.

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Transmigration of Neural Stem Cells across the Blood Brain Barrier Induced by Glioma Cells

PLoS ONE ◽

10.1371/journal.pone.0060655 ◽

2013 ◽

Vol 8 (4) ◽

pp. e60655 ◽

Cited By ~ 29

Author(s):

Mónica Díaz-Coránguez ◽

José Segovia ◽

Adolfo López-Ornelas ◽

Henry Puerta-Guardo ◽

Juan Ludert ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Blood Brain Barrier ◽

Glioma Cells ◽

Brain Barrier ◽

Blood Brain

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Inactivation of the ATMIN/ATM pathway protects against glioblastoma formation

eLife ◽

10.7554/elife.08711 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 9

Author(s):

Sophia M Blake ◽

Stefan H Stricker ◽

Hanna Halavach ◽

Anna R Poetsch ◽

George Cresswell ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Neural Development ◽

Combined Treatment ◽

Glioma Cells ◽

Wild Type ◽

Genetic Inactivation ◽

Primary Glioma ◽

Human Gbm ◽

Atm Signaling

Glioblastoma multiforme (GBM) is the most aggressive human primary brain cancer. Using a Trp53-deficient mouse model of GBM, we show that genetic inactivation of the Atm cofactor Atmin, which is dispensable for embryonic and adult neural development, strongly suppresses GBM formation. Mechanistically, expression of several GBM-associated genes, including Pdgfra, was normalized by Atmin deletion in the Trp53-null background. Pharmacological ATM inhibition also reduced Pdgfra expression, and reduced the proliferation of Trp53-deficient primary glioma cells from murine and human tumors, while normal neural stem cells were unaffected. Analysis of GBM datasets showed that PDGFRA expression is also significantly increased in human TP53-mutant compared with TP53-wild-type tumors. Moreover, combined treatment with ATM and PDGFRA inhibitors efficiently killed TP53-mutant primary human GBM cells, but not untransformed neural stem cells. These results reveal a new requirement for ATMIN-dependent ATM signaling in TP53-deficient GBM, indicating a pro-tumorigenic role for ATM in the context of these tumors.

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Abstract 5148: A neural stem cells marker fatty acid binding protein 7 (FABP7) is involved in proliferation and invasion of glioblastoma cells

10.1158/1538-7445.am10-5148 ◽

2010 ◽

Author(s):

Antonella De Rosa ◽

Marco Rossi ◽

Serena Pellegatta ◽

Patrizia Tunici ◽

Federico Malusa ◽

...

Keyword(s):

Stem Cells ◽

Fatty Acid ◽

Neural Stem Cells ◽

Fatty Acid Binding Protein ◽

Binding Protein ◽

Glioblastoma Cells ◽

Fatty Acid Binding ◽

Acid Binding Protein ◽

Marker Fatty Acid ◽

Proliferation And Invasion

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MAP Kinase Signaling Differences between Neural Stem Cells and Glioma Cells Provide a Mechanism for Selective Neuroprotection During Cranial Irradiation

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2014.05.621 ◽

2014 ◽

Vol 90 (1) ◽

pp. S148

Author(s):

A. Stessin ◽

M. Banu ◽

J.A. Boockvar ◽

B. Parashar ◽

A.G. Wernicke ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Map Kinase ◽

Glioma Cells ◽

Cranial Irradiation ◽

Kinase Signaling ◽

Map Kinase Signaling

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Reciprocal effects of conditioned medium on cultured glioma cells and neural stem cells

Journal of Clinical Neuroscience ◽

10.1016/j.jocn.2009.04.009 ◽

2009 ◽

Vol 16 (12) ◽

pp. 1619-1623 ◽

Cited By ~ 6

Author(s):

Fu Xue Chen ◽

Wen Wen Ren ◽

Yang Yang ◽

Di Shen ◽

Yijia Zong ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Conditioned Medium ◽

Glioma Cells ◽

Reciprocal Effects

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Meta-analysis of whole-genome gene expression datasets assessing the effects of IDH1 and IDH2 mutations in isogenic disease models

Scientific Reports ◽

10.1038/s41598-021-04214-7 ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Hans-Juergen Schulten ◽

Fatima Al-Adwani ◽

Haneen A. Bin Saddeq ◽

Heba Alkhatabi ◽

Nofe Alganmi ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Expression Profiles ◽

Meta Analysis ◽

Glioma Cells ◽

Heart Tissue ◽

Disease Models ◽

Signal Molecules ◽

Mouse Heart ◽

Idh Mutations

AbstractMutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are oncogenic drivers to a variable extent in several tumors, including gliomas, acute myeloid leukemia (AML), cholangiocarcinoma, melanoma, and thyroid carcinoma. The pathobiological effects of these mutations vary considerably, impeding the identification of common expression profiles. We performed an expression meta-analysis between IDH-mutant (IDHmut) and IDH-wild-type (IDHwt) conditions in six human and mouse isogenic disease models. The datasets included colon cancer cells, glioma cells, heart tissue, hepatoblasts, and neural stem cells. Among differentially expressed genes (DEGs), serine protease 23 (PRSS23) was upregulated in four datasets, i.e., in human colon carcinoma cells, mouse heart tissue, mouse neural stem cells, and human glioma cells. Carbonic anhydrase 2 (CA2) and prolyl 3-hydroxylase 2 (P3H2) were upregulated in three datasets, and SOX2 overlapping transcript (SOX2-OT) was downregulated in three datasets. The most significantly overrepresented protein class was termed intercellular signal molecules. An additional DEG set contained genes that were both up- and downregulated in different datasets and included oxidases and extracellular matrix structural proteins as the most significantly overrepresented protein classes. In conclusion, this meta-analysis provides a comprehensive overview of the expression effects of IDH mutations shared between different isogenic disease models. The generated dataset includes biomarkers, e.g., PRSS23 that may gain relevance for further research or clinical applications in IDHmut tumors.

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