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
-
Integrins as A New Target for Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Diabetes-induced Epigenetic Signature in Vascular Cells
Endocrine, Metabolic & Immune Disorders - Drug Targets Targeting Autophagic Pathways by Plant Natural Compounds in Cancer Treatment
Current Drug Targets Noble metal-dithiocarbamates precious allies in the fight against cancer
Mini-Reviews in Medicinal Chemistry C-20 Cyclopropyl Vitamin D3 Analogs
Current Topics in Medicinal Chemistry Venous Collateral Circulation of the Extracranial Cerebrospinal Outflow Routes
Current Neurovascular Research The Role of DNA Methylation in the Pathogenesis and Treatment of Cancer
Current Clinical Pharmacology Neuroproteomics: Are We Biased in Our Representation of Molecular Targets Associated with Specific Domains? Implications in Biomarker Discovery
Current Proteomics Nanoparticles in Melanoma
Current Medicinal Chemistry The Many Faces of Glutathione Transferase Pi
Current Molecular Medicine The Recent Development of Farnesyltransferase Inhibitors as Anticancer and Antimalarial Agents
Mini-Reviews in Medicinal Chemistry Biocombinatorial Selection of Carbohydrate Binding Agents of Therapeutic Significance
Current Drug Discovery Technologies Peptides, Proteins and Peptide/Protein-Polymer Conjugates as Drug Delivery System
Protein & Peptide Letters Curcumin Targets in Inflammation and Cancer
Endocrine, Metabolic & Immune Disorders - Drug Targets Perturbation of HSP Network in MCF-7 Breast Cancer Cell Line Triggers Inducible HSP70 Expression and Leads to Tumor Suppression
Anti-Cancer Agents in Medicinal Chemistry The Role of Melanocortin Peptides and Receptors in Regulation of Energy Balance
Current Pharmaceutical Design Enzymes To Die For: Exploiting Nucleotide Metabolizing Enzymes for Cancer Gene Therapy
Current Gene Therapy The use of Azoles Containing Natural Products in Cancer Prevention and Treatment: An Overview
Anti-Cancer Agents in Medicinal Chemistry Proteomic Approaches in Plant Biology
Current Proteomics Glyceraldehyde-3-phosphate Dehydrogenase from Chironomidae Showed Differential Activity Towards Metals
Protein & Peptide Letters