Abstract
Glioblastomas are highly lethal cancers for which conventional therapies provide only palliation. The cellular heterogeneity of glioblastomas is manifest in genetic and epigenetic variation with both stochastic and hierarchical models informing cellular phenotypes. At the apex of the hierarchy is a self-renewing, tumorigenic, cancer stem cell (CSC). The significance of CSCs is underscored by their resistance to cytotoxic therapies, invasive potential, and promotion of angiogenesis. Thus, targeting CSCs may offer therapeutic benefit and sensitize tumors to conventional treatment, demanding elucidation of CSC regulation. Attention has been paid to intrinsic cellular systems in CSCs, but recognition of extrinsic factors is evolving. Glioma stem cells (GSCs) are enriched in functional niches-prominently the perivascular space and hypoxic regions. These niches provide instructive cues to maintain GSCs and induce cellular plasticity towards a stem-like phenotype. GSC-maintaining niches may therefore offer novel therapeutic targets but also signal additional complexity with perhaps different pools of GSCs governed by different molecular mechanisms that must be targeted for tumor control.
Keywords: Glioma stem cell, cancer stem cell, microenvironment, glioma, vascular endothelial growth factor, stromal-derived factor 1, CD133, glycosylation, angiogenesis, digoxin
Current Pharmaceutical Design
Title: Glioma Stem Cell Maintenance: The Role of the Microenvironment
Volume: 17 Issue: 23
Author(s): John M. Heddleston, Masahiro Hitomi, Monica Venere, William A. Flavahan, Kenneth Yang, Youngmi Kim, Sana Minhas, Jeremy N. Rich and Anita B. Hjelmeland
Affiliation:
Keywords: Glioma stem cell, cancer stem cell, microenvironment, glioma, vascular endothelial growth factor, stromal-derived factor 1, CD133, glycosylation, angiogenesis, digoxin
Abstract: Glioblastomas are highly lethal cancers for which conventional therapies provide only palliation. The cellular heterogeneity of glioblastomas is manifest in genetic and epigenetic variation with both stochastic and hierarchical models informing cellular phenotypes. At the apex of the hierarchy is a self-renewing, tumorigenic, cancer stem cell (CSC). The significance of CSCs is underscored by their resistance to cytotoxic therapies, invasive potential, and promotion of angiogenesis. Thus, targeting CSCs may offer therapeutic benefit and sensitize tumors to conventional treatment, demanding elucidation of CSC regulation. Attention has been paid to intrinsic cellular systems in CSCs, but recognition of extrinsic factors is evolving. Glioma stem cells (GSCs) are enriched in functional niches-prominently the perivascular space and hypoxic regions. These niches provide instructive cues to maintain GSCs and induce cellular plasticity towards a stem-like phenotype. GSC-maintaining niches may therefore offer novel therapeutic targets but also signal additional complexity with perhaps different pools of GSCs governed by different molecular mechanisms that must be targeted for tumor control.
Export Options
About this article
Cite this article as:
M. Heddleston John, Hitomi Masahiro, Venere Monica, A. Flavahan William, Yang Kenneth, Kim Youngmi, Minhas Sana, N. Rich Jeremy and B. Hjelmeland Anita, Glioma Stem Cell Maintenance: The Role of the Microenvironment, Current Pharmaceutical Design 2011; 17 (23) . https://dx.doi.org/10.2174/138161211797249260
DOI https://dx.doi.org/10.2174/138161211797249260 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
?Revolutionizing Cancer Treatment: Nano-Therapeutics Targeting Tumor Microenvironment?
This thematic issue explores the forefront of cancer treatment, centering on the groundbreaking potential of nano-therapeutics meticulously designed to target the tumor microenvironment. At its core, the issue aims to unravel the latest advancements in nanotechnology, showcasing innovative materials, formulations, and delivery systems that hold promise for redefining cancer therapeutics. ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
MDM2 Increases Drug Resistance in Cancer Cells by Inducing EMT Independent of p53
Current Medicinal Chemistry Editorial [Hot Topic: Gliomas: Current Issues in Diagnosis and Treatment (Guest Editor: Stephan Ulmer)]
Current Medical Imaging CCL2-CCR2 Signaling in Disease Pathogenesis
Endocrine, Metabolic & Immune Disorders - Drug Targets A Discussion Regarding the Application of the Hertz Contact Theory on Biological Samples in AFM Nanoindentation Experiments
Micro and Nanosystems Tumor-Associated Macrophages as Potential Targets for Anti-Cancer Activity of Marine Invertebrate-Derived Compounds
Current Pharmaceutical Design The Yin and Yang of microRNA Assay Methods
MicroRNA NUPR1 Interacts with p53, Transcriptionally Regulates p21 and Rescues Breast Epithelial Cells from Doxorubicin-Induced Genotoxic Stress
Current Cancer Drug Targets Sesamol Induces Apoptosis by Altering Expression of Bcl-2 and Bax Proteins and Modifies Skin Tumor Development in Balb/c Mice
Anti-Cancer Agents in Medicinal Chemistry Radiolabeled Glucose Derivatives for Tumor Imaging Using SPECT and PET
Current Medicinal Chemistry Recent Findings on the Application of Toll-like Receptors Agonists in Cancer Therapy
Current Medicinal Chemistry Use of Carbohydrate-Conjugated Nanoparticles for an Integrated Approach to Functional Imaging of Glycans and Understanding of their Molecular Mechanisms
Current Pharmaceutical Biotechnology The Action of Prostaglandins on Ion Channels
Current Neuropharmacology Clinical Applications of Choline PET/CT in Brain Tumors
Current Pharmaceutical Design Induction of Antitumor Immune Responses with Recombinant Lentivector: Role of Skin Derived DCs
Current Cancer Therapy Reviews p53 Regulation of Energy Metabolism and Mitochondria Regulation of p53 in Cancer Cells: An Insight into the Role of Manganese Superoxide Dismutase
Current Pharmaceutical Biotechnology Neurorescue Activity, APP Regulation and Amyloid-β Peptide Reduction by Novel Multi-Functional Brain Permeable Iron- Chelating- Antioxidants,M-30 and Green Tea Polyphenol, EGCG
Current Alzheimer Research Fungal Bioactive Compounds in Pharmaceutical Research and Development
Current Bioactive Compounds ABC Transporters as Potential Targets for Modulation of Drug Resistance
Mini-Reviews in Medicinal Chemistry Editorial [Hot Topic: TGF-β As Target in Oncology (Guest Editor: Karl-Hermann Schlingensiepen)]
Current Pharmaceutical Biotechnology Involvement of the Mitochondrial Benzodiazepine Receptor in Traumatic Brain Injury: Therapeutic Implications
CNS & Neurological Disorders - Drug Targets