Abstract
For many years, extracellular matrix (ECM) was considered to function as a tissue support and filler. However, we now know that ECM proteins control many cellular events through their interaction with cell-surface receptors and cytoplasmic signaling pathways. For example, they regulate cell proliferation, cell division, cell adhesion, cell migration, and apoptosis. We focus in this review on a laminin isoform, laminin-332 (formerly termed laminin-5), a major component of the basement membrane (BM) of skin and other epithelial tissues. It is composed of 3 subunits (α3, β3, and γ2) and interacts with at least two integrin receptors expressed by epithelial cells (α3β1 and α6β4 integrin). Mutations in either laminin-332 or integrin α6β4 result in junctional epidermolysis bullosa, a blistering skin disease, while targeting of laminin-332 by autoantibodies in cicatricial pemphigoid leads to dysadhesion of epithelial cells from their underlying connective tissue. Abnormal expression of laminin-332 and its integrin receptors is also a hallmark of certain tumor types and is believed to promote invasion of colon, breast and skin cancer cells. Moreover, there is emerging evidence that laminin-332 and its protease degradation products are not only found at the leading front of several tumors but also likely induce and/or promote tumor cell migration. Thus, in this review, we focus specifically on the role of laminin-332 and its integrin receptors in adhesion, proliferation, and migration/invasion of cancer cells. Finally, we discuss strategies for the development of laminin-332-based antagonists for the treatment of malignant tumors.
Keywords: Integrin, laminin, cancer, basement membrane, proteolysis, cell signaling, cell adhesion, gene expression
Current Medicinal Chemistry
Title: Laminin-332-Integrin Interaction: A Target For Cancer Therapy?
Volume: 15 Issue: 20
Author(s): Daisuke Tsuruta, Hiromi Kobayashi, Hisayoshi Imanishi, Koji Sugawara, Masamitsu Ishii and Jonathan C.R. Jones
Affiliation:
Keywords: Integrin, laminin, cancer, basement membrane, proteolysis, cell signaling, cell adhesion, gene expression
Abstract: For many years, extracellular matrix (ECM) was considered to function as a tissue support and filler. However, we now know that ECM proteins control many cellular events through their interaction with cell-surface receptors and cytoplasmic signaling pathways. For example, they regulate cell proliferation, cell division, cell adhesion, cell migration, and apoptosis. We focus in this review on a laminin isoform, laminin-332 (formerly termed laminin-5), a major component of the basement membrane (BM) of skin and other epithelial tissues. It is composed of 3 subunits (α3, β3, and γ2) and interacts with at least two integrin receptors expressed by epithelial cells (α3β1 and α6β4 integrin). Mutations in either laminin-332 or integrin α6β4 result in junctional epidermolysis bullosa, a blistering skin disease, while targeting of laminin-332 by autoantibodies in cicatricial pemphigoid leads to dysadhesion of epithelial cells from their underlying connective tissue. Abnormal expression of laminin-332 and its integrin receptors is also a hallmark of certain tumor types and is believed to promote invasion of colon, breast and skin cancer cells. Moreover, there is emerging evidence that laminin-332 and its protease degradation products are not only found at the leading front of several tumors but also likely induce and/or promote tumor cell migration. Thus, in this review, we focus specifically on the role of laminin-332 and its integrin receptors in adhesion, proliferation, and migration/invasion of cancer cells. Finally, we discuss strategies for the development of laminin-332-based antagonists for the treatment of malignant tumors.
Export Options
About this article
Cite this article as:
Tsuruta Daisuke, Kobayashi Hiromi, Imanishi Hisayoshi, Sugawara Koji, Ishii Masamitsu and Jones C.R. Jonathan, Laminin-332-Integrin Interaction: A Target For Cancer Therapy?, Current Medicinal Chemistry 2008; 15 (20) . https://dx.doi.org/10.2174/092986708785132834
DOI https://dx.doi.org/10.2174/092986708785132834 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Metastasis: Recent Discoveries and Novel Perioperative Treatment Strategies with Particular Interest in the Hemostatic Compound Desmopressin
Current Pharmaceutical Biotechnology Evaluating 3D-printed Bolus Compared to Conventional Bolus Types Used in External Beam Radiation Therapy
Current Medical Imaging Role of Cyclooxygenases in Angiogenesis
Current Medicinal Chemistry Advances of Metal Enhanced Fluorescence Applications for the Biomedical Field
Current Proteomics Progesterone Receptor Membrane Component 1 and its Accomplice: Emerging Therapeutic Targets in Lung Cancer
Endocrine, Metabolic & Immune Disorders - Drug Targets MET and ALK as Targets for the Treatment of NSCLC
Current Pharmaceutical Design Evidence for Anti-Cancer Properties of Blueberries: A Mini-Review
Anti-Cancer Agents in Medicinal Chemistry A Novel Therapeutic Approach in Acute Promyelocytic Leukemia with All-trans retinoic Acid and Cyclin-dependent Kinase Inhibitors
Clinical Cancer Drugs UV Induced Skin Immunosuppression
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Inhibiting HSP90 to Treat Cancer: A Strategy in Evolution
Current Molecular Medicine Glycogen Synthase Kinase-3 (GSK-3) Inhibitors as a New Lead for Treating Breast and Ovarian Cancer
Current Drug Targets Immunoregulatory and Effector Activities of Nitric Oxide and Reactive Nitrogen Species in Cancer
Current Medicinal Chemistry Targeting CD147 is a Novel Strategy for Antitumor Therapy
Current Pharmaceutical Design The Pim Kinases: New Targets for Drug Development
Current Drug Targets Targeted Drug Delivery Systems and Their Therapeutic Applications in Cancer and Immune Pathological Conditions
Infectious Disorders - Drug Targets Applications and Limitations of Genetically Modified Mouse Models in Drug Discovery and Development
Current Drug Metabolism Evaluation of Anticancer, Antibacterial and Antioxidant Properties of a Medicinally Treasured Fern Tectaria coadunata with its Phytoconstituents Analysis by HR-LCMS
Anti-Cancer Agents in Medicinal Chemistry Investigational Hypoxia-Activated Prodrugs: Making Sense of Future Development
Current Drug Targets The Antimitotic Potential of PARP Inhibitors, An Unexplored Therapeutic Alternative
Current Topics in Medicinal Chemistry Spindle Cell Metaplastic Breast Carcinoma
Current Medical Imaging