Abstract
β2-microglobulin (β2-m) has become the focus of intense scrutiny since the discovery of its undesirable roles promoting osteomimicry and cancer progression. β2-m is a well-known housekeeping protein that forms complexes with the heavy chain of major histocompatibility complex class I molecules, which are heterodimeric cell surface proteins that present antigenic peptides to cytotoxic T cells. On recognition of foreign peptide antigens on cell surfaces, T cells actively bind and lyse antigen-presenting cancer cells. In addition to its roles in tumor immunity, β2-m has two different functions in cancer cells, either tumor promoting or tumor suppressing, in cancer cell context-dependent manner. Our studies have demonstrated that β2-m is involved extensively in the functional regulation of growth, survival, apoptosis, and even metastasis of cancer cells. We found that β2-m is a soluble growth factor and a pleiotropic signaling molecule which interacts with its receptor, hemochromatosis protein, to modulate epithelial-to-mesenchymal transition (EMT) through iron-responsive pathways. Specific antibodies against β2-m have remarkable tumoricidal activity in cancer, through β2-m action on iron flux, alterations of intracellular reactive oxygen species, DNA damage and repair enzyme activities, β-catenin activation and cadherin switching, and tumor responsiveness to hypoxia. These novel functions of β2-m and β2-m signaling may be common to several solid tumors including human lung, breast, renal, and prostate cancers. Our experimental results could lead to the development of a novel class of antibody-based pharmaceutical agents for cancer growth control. In this review, we briefly summarize the recent data regarding β2-m as a promising new cancer therapeutic target and discuss antagonizing this therapeutic target with antibody therapy for the treatment of localized and disseminated cancers.
Keywords: Anti-β2-m antibody, apoptosis, β2-microglobulin (β2-m), osteomimicry.
Anti-Cancer Agents in Medicinal Chemistry
Title:β2-Microglobulin-mediated Signaling as a Target for Cancer Therapy
Volume: 14 Issue: 3
Author(s): Takeo Nomura, Wen-Chin Huang, Haiyen E. Zhau, Sajni Josson, Hiromitsu Mimata and Leland W. K. Chung
Affiliation:
Keywords: Anti-β2-m antibody, apoptosis, β2-microglobulin (β2-m), osteomimicry.
Abstract: β2-microglobulin (β2-m) has become the focus of intense scrutiny since the discovery of its undesirable roles promoting osteomimicry and cancer progression. β2-m is a well-known housekeeping protein that forms complexes with the heavy chain of major histocompatibility complex class I molecules, which are heterodimeric cell surface proteins that present antigenic peptides to cytotoxic T cells. On recognition of foreign peptide antigens on cell surfaces, T cells actively bind and lyse antigen-presenting cancer cells. In addition to its roles in tumor immunity, β2-m has two different functions in cancer cells, either tumor promoting or tumor suppressing, in cancer cell context-dependent manner. Our studies have demonstrated that β2-m is involved extensively in the functional regulation of growth, survival, apoptosis, and even metastasis of cancer cells. We found that β2-m is a soluble growth factor and a pleiotropic signaling molecule which interacts with its receptor, hemochromatosis protein, to modulate epithelial-to-mesenchymal transition (EMT) through iron-responsive pathways. Specific antibodies against β2-m have remarkable tumoricidal activity in cancer, through β2-m action on iron flux, alterations of intracellular reactive oxygen species, DNA damage and repair enzyme activities, β-catenin activation and cadherin switching, and tumor responsiveness to hypoxia. These novel functions of β2-m and β2-m signaling may be common to several solid tumors including human lung, breast, renal, and prostate cancers. Our experimental results could lead to the development of a novel class of antibody-based pharmaceutical agents for cancer growth control. In this review, we briefly summarize the recent data regarding β2-m as a promising new cancer therapeutic target and discuss antagonizing this therapeutic target with antibody therapy for the treatment of localized and disseminated cancers.
Export Options
About this article
Cite this article as:
Nomura Takeo, Huang Wen-Chin, Zhau E. Haiyen, Josson Sajni, Mimata Hiromitsu and Chung W. K. Leland, β2-Microglobulin-mediated Signaling as a Target for Cancer Therapy, Anti-Cancer Agents in Medicinal Chemistry 2014; 14 (3) . https://dx.doi.org/10.2174/18715206113139990092
DOI https://dx.doi.org/10.2174/18715206113139990092 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...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
Related Articles
-
Molecular Link Mechanisms between Inflammation and Cancer
Current Pharmaceutical Design Characterization of a New Allelic Variant of Triosephosphate Isomerase from the LNCaP Human Prostate Cancer Cell Line: Enzyme Inhibition and Spectroscopic Studies
Current Enzyme Inhibition Knowledge of Epigenetic Influence for Prostate Cancer Therapy
Current Cancer Drug Targets Phosphine-Gold(I) Compounds as Anticancer Agents: General Description and Mechanisms of Action
Anti-Cancer Agents in Medicinal Chemistry Peroxisome Proliferator-Activated Receptors: Role of Isoform Gamma in the Antineoplastic Effect of Iodine in Mammary Cancer
Current Cancer Drug Targets Stress Related Neuroendocrine Influences in Ovarian Cancer
Current Cancer Therapy Reviews A Review of Preclinical Experiments Toward Targeting M2 Macrophages in Prostate Cancer
Current Drug Targets Deoxypodophyllotoxin Isolated from Juniperus communis Induces Apoptosis in Breast Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry microRNA Biogenesis Pathway as a Therapeutic Target for Human Disease and Cancer
Current Pharmaceutical Design Alternative Splicing, DNA Damage and Modulating Drugs in Radiation Therapy for Cancer
Anti-Cancer Agents in Medicinal Chemistry Effect of Cytostatic Drugs on the mRNA Expression Levels of Ribonuclease κ in Breast and Ovarian Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Hypothalamic Glucose Sensing and Glycaemic Disease
Current Diabetes Reviews The Antagonists of Endothelin Receptors: Results and Perspectives
Current Pharmaceutical Analysis CBP-dependent Wnt/β-catenin signaling is crucial in regulation of MDR1 transcription
Current Cancer Drug Targets First Inhibitors of the Steroidogenic Enzyme Type 7 17β-Hydroxysteroid Dehydrogenase
Letters in Drug Design & Discovery Highlights on Medical Treatment of Uterine Fibroids
Current Pharmaceutical Design Valeriana jatamansi Constituent IVHD-valtrate As a Novel Therapeutic Agent to Human Ovarian Cancer: in vitro and in vivo Activities and Mechanisms
Current Cancer Drug Targets Incretin-Based Antidiabetic Agents for the Management of Non-Alcoholic Fatty Liver Disease
Current Vascular Pharmacology Antifungal Therapy of Aspergillosis of the Central Nervous System and Aspergillus Endophthalmitis
Current Pharmaceutical Design The Potential of Peroxisome Proliferator-Activated Receptor γ (PPARγ) Ligands in the Treatment of Hematological Malignancies
Mini-Reviews in Medicinal Chemistry