Brain tumor stem cells and the tumor microenvironment

2008 ◽  
Vol 24 (3-4) ◽  
pp. E27 ◽  
Author(s):  
Rahul Jandial ◽  
Hoisang U ◽  
Michael L. Levy ◽  
Evan Y. Snyder
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Brain Tumor ◽  
Cancer Stem Cells ◽  
Tumor Stem Cells ◽  
Tumor Environment ◽  
Brain Tumor Stem Cells ◽  
Differentiation And Proliferation ◽  
The Brain

✓ Recent advances in stem cell research and developmental neurobiology have uncovered new perspectives from which to investigate various forms of cancer. Specifically, the hypothesis that tumors consist of a subpopulation of malignant cells similar to stem cells is of great interest to scientists and clinicians and has been dubbed the “cancer stem cell hypothesis.” The region in which this assertion is most relevant is within the brain. Cancer stem cells have been isolated from brain tumors that exhibit characteristics of differentiation and proliferation normally seen only in neural stem cells. These cancer stem cells may be responsible for tumor origin, survival, and proliferation. Furthermore, these cells must be considered within their immediate microenvironment when investigating mechanisms of tumorigenesis. Evidence of brain tumor stem cells is reviewed along with the role of tumor environment as the context within which these cells should be understood.

scholarly journals TMIC-56. ROLE OF HUMAN BRAIN TUMOR STEM CELLS-DERIVED EXTRACELLULAR VESICLES ON THE PHENOTYPIC TRANSDIFFERENTIATION OF HUMAN NEURAL PROGENITOR CELLS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi260-vi260
Author(s):  
Natanael Zarco ◽  
Emily Norton ◽  
Montserrat Lara-Velazquez ◽  
Anna Carrano ◽  
Alfredo Quinones-Hinojosa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Tumor Microenvironment ◽  
Extracellular Vesicles ◽  
Primary Cultures ◽  
Adult Brain ◽  
Cell Subpopulation ◽  
Tumor Stem Cells ◽  
Brain Tumor Stem Cells

Abstract Glioblastoma (GBM) is the most aggressive of all the brain tumors with a median patient survival less than 15 months. Despite of surgical resection, radiotherapy, and chemotherapy, recurrence rate is almost 100%. A great percentage of GBM tumors (~60%) infiltrate and contact the ventricular-subventricular zone (V-SVZ). Interestingly, these tumors are the most aggressive, and invariably lead to higher distal recurrence rates, shorter time to tumor progression, and lower overall survival of the patient. The reason for this role of V-SVZ-proximity on the outcome of GBM patients is unknown. We suggest that a potential explanation is the interaction of GBM with the V-SVZ. This region is the largest neurogenic niche in the adult brain where neural stem cells (NSCs) give rise to newborn neuroblasts that migrate toward the olfactory bulb. In GBM there is a cell subpopulation called brain tumor stem cells (BTSCs) with NSCs-like characteristics, but with added potential for tumor initiation, recurrence and invasiveness. Tumor microenvironment plays an important role in migration and invasion process. In the present work, we used the total exosome isolation kit to purify Extracellular Vesicles (EVs) from human primary cultures of BTSCs. We determined that BTSCs-derived EVs contain specific information that is transfer to primary cultures of human Neural Progenitors Cells (NPCs) modulating their proliferation rate, cell viability, and migration. In addition, we identify that NPCs taken up BTSCs-derived EVs and significantly increase the expression levels of stemness-related genes such as Nestin, Nanog, and Sox2, suggesting that a phenotypic transdifferentiation is being carry out. These results support our hypothesis that GBM modulate the tumor microenvironment close to the V-SVZ by releasing EVs that target cellular components in this region and promote their phenotypic transformation, highlighting that NPCs biology changes in the context of tumor environment.

scholarly journals Examination of the Therapeutic Potential of Delta-24-RGD in Brain Tumor Stem Cells: Role of Autophagic Cell Death

2007 ◽  
Vol 99 (18) ◽  
pp. 1410-1414 ◽  
Author(s):  
Hong Jiang ◽  
Candelaria Gomez-Manzano ◽  
Hiroshi Aoki ◽  
Marta M.. Alonso ◽  
Seiji Kondo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Brain Tumor ◽  
Therapeutic Potential ◽  
Autophagic Cell Death ◽  
Tumor Stem Cells ◽  
Brain Tumor Stem Cells

scholarly journals Brain tumor stem cells: phenotypic characterization and directed therapeutic approaches

2015 ◽  
Vol 3 (2) ◽  
pp. 177-183
Author(s):  
L. Belska ◽  
M. Lisyany
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Intracellular Signaling ◽  
Phenotypic Characterization ◽  
Tumor Stem Cells ◽  
Therapeutic Approaches ◽  
Brain Tumor Stem Cells ◽  
The Brain ◽  
Methods Of Isolation

The review presents the current conceptions of the origin, methods of isolation and phenotypic characterization of the brain tumor stem cells. Phenotypic similarity in molecular markers between cancer and neural stem cells is shown. Therapeutic approaches of impact on the brain tumor stem cells and on the intracellular signaling pathways of cancer stem cells are described.

A NEUROSURGEON'S GUIDE TO STEM CELLS, CANCER STEM CELLS, AND BRAIN TUMOR STEM CELLS

Neurosurgery ◽  
2009 ◽  
Vol 65 (2) ◽  
pp. 237-250 ◽  
Author(s):  
Samuel H. Cheshier ◽  
M. Yashar S. Kalani ◽  
Michael Lim ◽  
Laurie Ailles ◽  
Steven L. Huhn ◽  
...  
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Cancer Stem Cells ◽  
Tumor Stem Cells ◽  
Brain Tumor Stem Cells

scholarly journals STEM-21. INVESTIGATING DOT1L AS AN EPIGENETIC VULNERABILITY IN BRAIN TUMOR STEM CELLS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi238-vi238
Author(s):  
Danielle Bozek ◽  
Graham MacLeod ◽  
Xiaoguang Hao ◽  
Nishani Rajakulendran ◽  
Moloud Ahmadi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Brain Tumor ◽  
Neural Stem Cells ◽  
Tumor Growth ◽  
Cell Lines ◽  
Histone Methyltransferase ◽  
Tumor Stem Cells ◽  
Self Renewal ◽  
Brain Tumor Stem Cells

Abstract Glioblastoma (GBM), the most common and aggressive primary adult brain cancer, is thought to be driven by a small subpopulation of brain tumor stem cells (BTSCs). BTSCs exhibit shared properties with normal stem cells such as self-renewal and multilineage differentiation. These stem cell properties have been proposed to underlie GBM tumorigenicity, treatment evasion and contribute to tumor heterogeneity. To investigate the biology underlying the stem cell properties of GBM, we compared gene essentiality profiles for a panel of BTSCs, fetal neural stem cells and non-GBM cell lines using a CRISPR Cas9 knockout library. Interestingly, from these screens, we identified the histone methyltransferase disrupter of telomeric silencing-1-like (DOT1L) as an essential gene for the growth of BTSCs and fetal neural stem cells but not for non-GBM cell lines. DOT1L is the only known histone methyltransferase responsible for histone 3 lysine 79 methylation, an epigenetic mark associated with active gene transcription. The role of this epigenetic regulator in BTSCs was investigated in depth using EPZ-5676, a clinically relevant small molecule inhibitor. Short-term treatment with EPZ-5676 in BTSCs showed minimal effects on cell viability but led to striking morphological changes, increased neuronal and astrocytic differentiation and a reduction in self-renewal. Longer treatment periods with EPZ-5676 led to a decrease in BTSC proliferation and an increase in apoptosis. Furthermore, BTSCs pretreated with EPZ-5676 led to slowed orthotopic tumor growth and improved overall survival in a SCID mouse model. Overall, these findings suggest DOT1L epigenetically regulates GBM stem cell properties and tumor growth. We are further investigating the mechanisms underlying DOT1L regulation of gene expression in BTSCs with the goal of improving the field’s understanding of epigenetics and the therapeutic implications of targeting epigenetic processes in GBM.

scholarly journals Glioma Revisited: From Neurogenesis and Cancer Stem Cells to the Epigenetic Regulation of the Niche

2012 ◽  
Vol 2012 ◽  
pp. 1-20 ◽  
Author(s):  
Felipe de Almeida Sassi ◽  
Algemir Lunardi Brunetto ◽  
Gilberto Schwartsmann ◽  
Rafael Roesler ◽  
Ana Lucia Abujamra
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cellular Proliferation ◽  
Survival Rates ◽  
Comprehensive Analysis ◽  
Heterogeneous Population ◽  
Aggressive Tumor ◽  
Epigenetic Modulation ◽  
The Brain

Gliomas are the most incident brain tumor in adults. This malignancy has very low survival rates, even when combining radio- and chemotherapy. Among the gliomas, glioblastoma multiforme (GBM) is the most common and aggressive type, and patients frequently relapse or become refractory to conventional therapies. The fact that such an aggressive tumor can arise in such a carefully orchestrated organ, where cellular proliferation is barely needed to maintain its function, is a question that has intrigued scientists until very recently, when the discovery of the existence of proliferative cells in the brain overcame such challenges. Even so, the precise origin of gliomas still remains elusive. Thanks to new advents in molecular biology, researchers have been able to depict the first steps of glioma formation and to accumulate knowledge about how neural stem cells and its progenitors become gliomas. Indeed, GBM are composed of a very heterogeneous population of cells, which exhibit a plethora of tumorigenic properties, supporting the presence of cancer stem cells (CSCs) in these tumors. This paper provides a comprehensive analysis of how gliomas initiate and progress, taking into account the role of epigenetic modulation in the crosstalk of cancer cells with their environment.

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