Molecular Pathogenesis of Adult Brain Tumors and the Role of Stem Cells

Brain tumor cases make up a significant part of the neurosurgery Oral Board Exam. A multitude of brain tumors exist and can be intraaxial or extraaxial. When considering a differential diagnosis for a brain lesion, infection, hematomas, infarctions, thrombosed aneurysms, inflammation, and demyelinating disease must be considered in addition to tumors. Common adult brain tumors consist of gliomas, meningiomas, metastases, and pituitary tumors. Management of brain tumors consists of understanding preoperative care, indications for surgery, surgical approaches, interpretation of preoperative and postoperative imaging, intraoperative and postoperative complications, and the role of adjuvant therapy, including chemotherapy and radiotherapy. Reviewing these essential points for the most common brain tumor cases and mastering the current treatment recommendations for common tumors will also be helpful for the boards.

Download Full-text

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

Neuro-Oncology ◽

10.1093/neuonc/noz175.1090 ◽

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.

Download Full-text

The Role of Neurodevelopmental Pathways in Brain Tumors

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.659055 ◽

2021 ◽

Vol 9 ◽

Author(s):

Rachel N. Curry ◽

Stacey M. Glasgow

Keyword(s):

Brain Tumor ◽

Brain Tumors ◽

Disease Progression ◽

Adult Brain ◽

Signaling Cascades ◽

Tumor Initiation ◽

Developmental Factors ◽

Developmental Signaling ◽

Cell Signaling Pathways

Disruptions to developmental cell signaling pathways and transcriptional cascades have been implicated in tumor initiation, maintenance and progression. Resurgence of aberrant neurodevelopmental programs in the context of brain tumors highlights the numerous parallels that exist between developmental and oncologic mechanisms. A deeper understanding of how dysregulated developmental factors contribute to brain tumor oncogenesis and disease progression will help to identify potential therapeutic targets for these malignancies. In this review, we summarize the current literature concerning developmental signaling cascades and neurodevelopmentally-regulated transcriptional programs. We also examine their respective contributions towards tumor initiation, maintenance, and progression in both pediatric and adult brain tumors and highlight relevant differentiation therapies and putative candidates for prospective treatments.

Download Full-text

THE ROLE OF VASCULAR MICROENVIRONMENT IN THE FORMATION AND DEVELOPMENT OF BRAIN TUMORS

Problems in oncology ◽

10.37469/0507-3758-2018-64-5-570-577 ◽

2018 ◽

Vol 64 (5) ◽

pp. 570-577

Author(s):

Aleksandr Dorosevich ◽

N. Buzgan

Keyword(s):

Stem Cells ◽

Brain Tumors ◽

Tumor Cells ◽

Cell Lines ◽

Crucial Role ◽

Tumor Stem Cells ◽

Intercellular Interactions ◽

Resident Cell ◽

The Brain

Processes of neovascularization are key for the growth and spread of tumor cells. This article describes unique patterns of angiogenesis, which are considered as specific exclusively for brain tumors. At present the role of specialized perivascular niches in the development of oncological processes of the brain acquires a growing importance in the eyes of researchers. Perivascular niches play a crucial role in intercellular interactions between resident cell lines in the development of the tumor process and are also a source of tumor stem cells.

Download Full-text

Role of cancer stem cells in brain tumors

BioMedicine ◽

10.1016/j.biomed.2012.06.001 ◽

2012 ◽

Vol 2 (3) ◽

pp. 84-91 ◽

Cited By ~ 6

Author(s):

Ya-Huey Chen ◽

Mien-Chie Hung ◽

Woei-Cherng Shyu

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Brain Tumors

Download Full-text

The more you have, the less you get: the functional role of inflammation on neuronal differentiation of endogenous and transplanted neural stem cells in the adult brain

Journal of Neurochemistry ◽

10.1111/j.1471-4159.2009.06548.x ◽

2010 ◽

Vol 112 (6) ◽

pp. 1368-1385 ◽

Cited By ~ 57

Author(s):

Patricia Mathieu ◽

Daniela Battista ◽

Amaicha Depino ◽

Valeria Roca ◽

Mariana Graciarena ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Neuronal Differentiation ◽

Functional Role ◽

Adult Brain

Download Full-text

STEM CELL THERAPY OF MALIGNANT BRAIN TUMORS: REALITY AND PROSPECTS

Clinical Practice ◽

10.17816/clinpract4445-54 ◽

2013 ◽

Vol 4 (4) ◽

pp. 45-54

Author(s):

I S Bryukhovetskiy ◽

A S Bryukhovetskiy ◽

P V Mischenko ◽

I A Merkulov ◽

Y S Khotimchenko

Keyword(s):

Stem Cells ◽

Brain Tumors ◽

Malignant Tumors ◽

Traumatic Injury ◽

The Body ◽

Malignant Brain Tumors ◽

Hypoxic Zone ◽

Tumor Center ◽

Neoplastic Process

Modern methods for the treatment of malignant brain tumors are insufficiently effective. One reason for this is that the existing technologies and methods are focused on removing all neoplastic cellsfrom the body. Understanding the mechanisms of systemic migration of stem cells provides a new view on the role of this phenomenon in the development of malignant tumors. Migration and homing of normal stem cells, being originally the regulatory process, ensuring revascularization and remodeling of ischemic or traumatic injury of brain, play a role of the axial conductor of neoplastic process in carcinogenesis. The use of the phenomenon of migration and homing of stem cells in the tumor center for therapeutic purposes opens the possibility of overcoming the blood-brain barrier, reducing the toxicity of chemotherapy and increasing the radiation therapy efficiency, makes possible the directed influence on the hypoxic zone of the tumor, can directly affect to the key life processes of tumor stem cells. These arguments allow to consider the mechanisms of systemic migration and homing of stem cells to neoplastic foci as a fundamental theoretical platform for the creation of a fundamentally new class of anti-cancer, cell personalized medicines.

Download Full-text

Brain Tumors: Role of Neural Cancer Stem Cells

Stem Cells and Cancer Stem Cells, Volume 1 ◽

10.1007/978-94-007-1709-1_6 ◽

2011 ◽

pp. 49-57

Author(s):

M. Yashar S. Kalani ◽

Maziyar A. Kalani ◽

Victor C.K. Tse

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Brain Tumors

Download Full-text

Novel Roles of Small Extracellular Vesicles in Regulating the Quiescence and Proliferation of Neural Stem Cells

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.762293 ◽

2021 ◽

Vol 9 ◽

Author(s):

Jingtian Zhang ◽

Junki Uchiyama ◽

Koshi Imami ◽

Yasushi Ishihama ◽

Ryoichiro Kageyama ◽

...

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Gene Ontology ◽

Extracellular Vesicles ◽

Protein Translation ◽

Adult Brain ◽

Differentially Expressed Proteins ◽

Complex Processes ◽

G0 Phase

Neural stem cell (NSC) quiescence plays pivotal roles in avoiding exhaustion of NSCs and securing sustainable neurogenesis in the adult brain. The maintenance of quiescence and transition between proliferation and quiescence are complex processes associated with multiple niche signals and environmental stimuli. Exosomes are small extracellular vesicles (sEVs) containing functional cargos such as proteins, microRNAs, and mRNAs. The role of sEVs in NSC quiescence has not been fully investigated. Here, we applied proteomics to analyze the protein cargos of sEVs derived from proliferating, quiescent, and reactivating NSCs. Our findings revealed fluctuation of expression levels and functional clusters of gene ontology annotations of differentially expressed proteins especially in protein translation and vesicular transport among three sources of exosomes. Moreover, the use of exosome inhibitors revealed exosome contribution to entrance into as well as maintenance of quiescence. Exosome inhibition delayed entrance into quiescence, induced quiescent NSCs to exit from the G0 phase of the cell cycle, and significantly upregulated protein translation in quiescent NSCs. Our results suggest that NSC exosomes are involved in attenuating protein synthesis and thereby regulating the quiescence of NSCs.

Download Full-text

Therapeutic Potential of Neurotrophic Factors and Neural Stem Cells Against Ischemic Brain Injury

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200010000-00001 ◽

2000 ◽

Vol 20 (10) ◽

pp. 1393-1408 ◽

Cited By ~ 153

Author(s):

Koji Abe

Keyword(s):

Stem Cells ◽

Brain Injury ◽

Neural Stem Cells ◽

Neurotrophic Factors ◽

Therapeutic Potential ◽

Stem Cell Differentiation ◽

Adult Brain ◽

Ischemic Brain Injury ◽

Ischemic Brain

Development of neuronal and glial cells and their maintenance are under control of neurotrophic factors (NTFs). An exogenous administration of NTFs protects extremely sensitive brain tissue from ischemic damage. On the other hand, it is now known that neural stem cells are present in normal adult brain, and have a potential to compensate and recover neural functions that were lost due to ischemic stroke. These stem cells are also under control of NTFs to differentiate into a certain species of neural cells. Thus, the purpose of this review is to summarize the present understanding of the role of NTFs in normal and ischemic brain and the therapeutic potential of NTF protein itself or gene therapy, and then to summarize the role of NTFs in stem cell differentiation and a possible therapeutic potential with the neural stem cells against ischemic brain injury.

Download Full-text