Abstract
Hypoxia or oxygen deficiency is a salient feature of solid tumors. Hypoxic tumors are often resistant to conventional cancer therapies, and tumor hypoxia correlates with advanced stages of malignancy. Hypoxic tumors appear to be poorly differentiated. Increasing evidence suggests that hypoxia has the potential to inhibit tumor cell differentiation and thus plays a direct role in the maintenance of cancer stem cells. Studies have also shown that hypoxia blocks differentiation of mesenchymal stem/progenitor cells, a potential source of tumor-associated stromal cells. It is therefore likely that hypoxia may have a profound impact on the evolution of the tumor stromal microenvironment. These observations have led to the emergence of a novel paradigm for a role of hypoxia in facilitating tumor progression. Hypoxia may help create a microenvironment enriched in poorly differentiated tumor cells and undifferentiated stromal cells. Such an undifferentiated hypoxic microenvironment may provide essential cellular interactions and environmental signals for the preferential maintenance of cancer stem cells. This hypothesis suggests that effectively targeting hypoxic cancer stem cells is a key to successful tumor control.
Keywords: Cancer stem cells, differentiation, hypoxia, oxygen, tumor microenvironment
Current Molecular Medicine
Title: Hypoxic Tumor Microenvironment and Cancer Cell Differentiation
Volume: 9 Issue: 4
Author(s): Yuri Kim, Qun Lin, Peter M. Glazer and Zhong Yun
Affiliation:
Keywords: Cancer stem cells, differentiation, hypoxia, oxygen, tumor microenvironment
Abstract: Hypoxia or oxygen deficiency is a salient feature of solid tumors. Hypoxic tumors are often resistant to conventional cancer therapies, and tumor hypoxia correlates with advanced stages of malignancy. Hypoxic tumors appear to be poorly differentiated. Increasing evidence suggests that hypoxia has the potential to inhibit tumor cell differentiation and thus plays a direct role in the maintenance of cancer stem cells. Studies have also shown that hypoxia blocks differentiation of mesenchymal stem/progenitor cells, a potential source of tumor-associated stromal cells. It is therefore likely that hypoxia may have a profound impact on the evolution of the tumor stromal microenvironment. These observations have led to the emergence of a novel paradigm for a role of hypoxia in facilitating tumor progression. Hypoxia may help create a microenvironment enriched in poorly differentiated tumor cells and undifferentiated stromal cells. Such an undifferentiated hypoxic microenvironment may provide essential cellular interactions and environmental signals for the preferential maintenance of cancer stem cells. This hypothesis suggests that effectively targeting hypoxic cancer stem cells is a key to successful tumor control.
Export Options
About this article
Cite this article as:
Kim Yuri, Lin Qun, Glazer M. Peter and Yun Zhong, Hypoxic Tumor Microenvironment and Cancer Cell Differentiation, Current Molecular Medicine 2009; 9 (4) . https://dx.doi.org/10.2174/156652409788167113
DOI https://dx.doi.org/10.2174/156652409788167113 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
- 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
Related Articles
-
Na+-H+ Exchanger, pH Regulation and Cancer
Recent Patents on Anti-Cancer Drug Discovery Artemisinin, Promising Lead Natural Product for Various Drug Developments
Mini-Reviews in Medicinal Chemistry The Monoaminergic Tripartite Synapse: A Putative Target for Currently Available Antidepressant Drugs
Current Drug Targets Mast Cells and Basophils: Trojan Horses of Conventional Lin- Stem/Progenitor Cell Isolates
Current Pharmaceutical Design Fluorescence Molecular Imaging of Small Animal Tumor Models
Current Molecular Medicine Targeting miR-21 Induces Autophagy and Chemosensitivity of Leukemia Cells
Current Drug Targets Radiolabeled Probes Targeting G-Protein-Coupled Receptors for Personalized Medicine
Current Pharmaceutical Design Natural Compounds as Anticancer Agents Targeting DNA Topoisomerases
Current Genomics Targeting the Endocannabinod System to Limit Myocardial and Cerebral Ischemic and Reperfusion Injury
Current Pharmaceutical Biotechnology Targeting the Voltage-Dependent K+ Channels Kv1.3 and Kv1.5 as Tumor Biomarkers for Cancer Detection and Prevention
Current Medicinal Chemistry Anaplastic Lymphoma Kinase as a Therapeutic Target in Anaplastic Large Cell Lymphoma, Non-Small Cell Lung Cancer and Neuroblastoma
Anti-Cancer Agents in Medicinal Chemistry Impact of MCP -1 in Atherosclerosis
Current Pharmaceutical Design Interpreting the Mechanisms by which Integrins Promote the Differentiation of Mesenchymal Stem Cells and Integrin Application Prospects
Current Stem Cell Research & Therapy Therapeutic Targeting of Developmental Signaling Pathways in Medulloblastoma: Hedgehog, Notch, Wnt and Myc
Current Signal Transduction Therapy Neuroprotective Role of Hypothermia in Hypoxic-ischemic Brain Injury: Combined Therapies using Estrogen
Current Neuropharmacology SnoN: Bridging Neurobiology and Cancer Biology
Current Molecular Medicine Fluorescein Fluorescence Use in the Management of Intracranial Neoplastic and Vascular Lesions: A Review and Report of a New Technique
Current Drug Discovery Technologies Network Pharmacology and Reverse Molecular Docking-Based Prediction of the Molecular Targets and Pathways for Avicularin Against Cancer
Combinatorial Chemistry & High Throughput Screening Cyclic ADP-ribose (cADPR) and Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP): Novel Regulators of Ca 2+-Signaling and Cell Function
Current Molecular Medicine Preservation of Cellular Glutathione Status and Mitochondrial Membrane Potential by N-Acetylcysteine and Insulin Sensitizers Prevent Carbonyl Stress-Induced Human Brain Endothelial Cell Apoptosis
Current Neurovascular Research