Abstract
Chemokines and chemokine receptors play diverse roles in homeostasis. The chemokine stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 have critical functions in the immune, circulatory, and central nervous systems and have also been implicated in tumor biology and metastasis. Here we review the current data regarding the role of the CXCR4/SDF-1 chemokine axis in the development of bone metastases, derived from tumor models of breast or prostate cancers. There is substantial evidence that CXCR4 and SDF-1 directly influence the survival and proliferation of tumor cells. In regards to bone metastases, the CXCR4/SDF-1 axis also appears to facilitate tumor cell recruitment to the bone marrow microenvironment via a homing mechanism. This makes disruption of the chemokine axis an attractive therapeutic target for the prevention of tumor cell spread to bone. However, within the bone microenvironment, SDF-1 and CXCR4 appear to have conflicting roles. While genetic disruption of CXCR4 enhances osteoclast activity and therefore stimulates tumor cell growth in the bone - likely via release of bone-derived growth factors - SDF-1 has been shown to have either a stimulatory effect or no effect on osteoclasts. In short, the effects of the CXCR4/SDF-1 axis on tumor cell growth within the bone are not yet fully defined. Further, there are theoretical risks that blockade of this chemokine axis could impair immune function or mobilize tumor cells leading to other sites of metastasis. As such, caution should be taken when designing therapeutic strategies targeting this chemokine axis.
Keywords: Chemokines, CXCR4, SDF-1, bone metastasis, breast cancer, prostate cancer
Current Pharmaceutical Design
Title: The CXCR4/SDF-1 Chemokine Axis: A Potential Therapeutic Target for Bone Metastases?
Volume: 16 Issue: 11
Author(s): A.C. Hirbe, E.A. Morgan and K.N. Weilbaecher
Affiliation:
Keywords: Chemokines, CXCR4, SDF-1, bone metastasis, breast cancer, prostate cancer
Abstract: Chemokines and chemokine receptors play diverse roles in homeostasis. The chemokine stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 have critical functions in the immune, circulatory, and central nervous systems and have also been implicated in tumor biology and metastasis. Here we review the current data regarding the role of the CXCR4/SDF-1 chemokine axis in the development of bone metastases, derived from tumor models of breast or prostate cancers. There is substantial evidence that CXCR4 and SDF-1 directly influence the survival and proliferation of tumor cells. In regards to bone metastases, the CXCR4/SDF-1 axis also appears to facilitate tumor cell recruitment to the bone marrow microenvironment via a homing mechanism. This makes disruption of the chemokine axis an attractive therapeutic target for the prevention of tumor cell spread to bone. However, within the bone microenvironment, SDF-1 and CXCR4 appear to have conflicting roles. While genetic disruption of CXCR4 enhances osteoclast activity and therefore stimulates tumor cell growth in the bone - likely via release of bone-derived growth factors - SDF-1 has been shown to have either a stimulatory effect or no effect on osteoclasts. In short, the effects of the CXCR4/SDF-1 axis on tumor cell growth within the bone are not yet fully defined. Further, there are theoretical risks that blockade of this chemokine axis could impair immune function or mobilize tumor cells leading to other sites of metastasis. As such, caution should be taken when designing therapeutic strategies targeting this chemokine axis.
Export Options
About this article
Cite this article as:
Hirbe A.C., Morgan E.A. and Weilbaecher K.N., The CXCR4/SDF-1 Chemokine Axis: A Potential Therapeutic Target for Bone Metastases?, Current Pharmaceutical Design 2010; 16 (11) . https://dx.doi.org/10.2174/138161210791034012
DOI https://dx.doi.org/10.2174/138161210791034012 |
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
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
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Tumor Angiogenesis: A Potential Target In Cancer Control by Phytochemicals
Current Cancer Drug Targets High-Dose Linoleic Acid Activated JAK2-STAT3 Signaling Pathway Involved in Cytokine Production and Lipogenesis in Pancreatic Exocrine Cells
Current Molecular Medicine Newly Identified Tumor Antigens as Promising Cancer Vaccine Targets for Malignant Melanoma Treatment
Current Topics in Medicinal Chemistry Mutual Modulation of Femarelle and Vitamin D Analog Activities in Human Derived Female Cultured Osteoblasts
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Multiple Hsp70 Isoforms in the Eukaryotic Cytosol: Mere Redundancy or Functional Specificity?
Current Genomics Molecular Biological Roles of Ursolic Acid in the Treatment of Human Diseases
Current Bioactive Compounds The Functions of Histone Modification Enzymes in Cancer
Current Protein & Peptide Science Small Molecules and Future Regenerative Medicine
Current Topics in Medicinal Chemistry Targeting Epigenetics in Nervous System Disease
CNS & Neurological Disorders - Drug Targets Imaging Studies in Hypercalcemia
Current Medicinal Chemistry The FKBP51-Glucocorticoid Receptor Balance in Stress-Related Mental Disorders
Current Molecular Pharmacology SOCS6 Functions as a Tumor Suppressor by Inducing Apoptosis and Inhibiting Angiogenesis in Human Prostate Cancer
Current Cancer Drug Targets Rotundic Acid Regulates the Effects of Let-7f-5p on Caco2 Cell Proliferation
Anti-Cancer Agents in Medicinal Chemistry Steroid Receptor Ligands for Breast Cancer Targeting: An Insight into Their Potential Role As Pet Imaging Agents
Current Medicinal Chemistry Neuroimmune Interactions and Psychologycal Stress Induced by Cohabitation with a Sick Partner: A Review
Current Pharmaceutical Design Therapies of Hematological Malignancies: An Overview of the Potential Targets and Their Inhibitors
Current Chemical Biology Tipping the Balance Between Life and Death: Targeting Histone Acetylation for Cancer Therapy
Drug Delivery Letters Alphavirus Vectors for Gene Therapy Applications
Current Gene Therapy In Vivo Inhibition of the Estrogen Sulfatase Enzyme and Growth of DMBA-Induced Mammary Tumors by Melatonin
Current Cancer Drug Targets Review of the Biological Activity of Maslinic Acid
Current Drug Targets