Abstract
Anchorage-independent growth, anoikis resistance, and most steps of metastasis formation are integrin-mediated or -dependent processes, which are characteristics of malignant tumor cells. Acting as oncogenes or tumor suppressor genes, integrins may be involved in the oncogenic transformation of normal cells and their growth into a primary tumor node. During tumorigenesis, a switch of integrin expression can be observed, inasmuch as growth-promoting and growth-attenuating integrins are up- and down-regulated, respectively. ECM-ligand binding to an integrin initiates signals, which eradiating from the integrins are transmitted via different yet interconnecting pathways and elicit various cell functions, such as morphological changes, adhesion, migration and gene activation. Any of these functions takes part in the metastatic cascade of tumor progression, such as epithelial-to-mesenchymal transition of carcinoma cells, tumor cell contact with the basement membrane, invasion into neighboring tissues as well as production and activation of ECM-degrading MMPs. Besides their direct involvement in tumor progression as cell surface molecules on tumor cells, integrins in normal cells surrounding a tumor, e.g. endothelial cells, can also determine various cancer characteristics, such as tumor-induced neoangiogenesis and immune resistance. Hence, integrins are relevant pharmacological targets in tumor biology. Spurred by the recent success to generate pharmaceutical mimetics of RGD-dependent integrins and by the integrins easy accessibility on the cell surface, the hope is rising that also RGD-independent integrins, such as the collagen- and laminin-binding integrins, can be pharmacologically manipulated to fight integrin-dependent functions of cancer cells, which are necessary and at least partially specific for their proliferation and progression
Keywords: Integrin, extracellular matrix, tumorigenesis, metastasis, tumor progression, tumor-induced angiogenesis
Current Cancer Drug Targets
Title: Integrins in Cancer Treatment
Volume: 6 Issue: 2
Author(s): Johannes A. Eble and Jorg Haier
Affiliation:
Keywords: Integrin, extracellular matrix, tumorigenesis, metastasis, tumor progression, tumor-induced angiogenesis
Abstract: Anchorage-independent growth, anoikis resistance, and most steps of metastasis formation are integrin-mediated or -dependent processes, which are characteristics of malignant tumor cells. Acting as oncogenes or tumor suppressor genes, integrins may be involved in the oncogenic transformation of normal cells and their growth into a primary tumor node. During tumorigenesis, a switch of integrin expression can be observed, inasmuch as growth-promoting and growth-attenuating integrins are up- and down-regulated, respectively. ECM-ligand binding to an integrin initiates signals, which eradiating from the integrins are transmitted via different yet interconnecting pathways and elicit various cell functions, such as morphological changes, adhesion, migration and gene activation. Any of these functions takes part in the metastatic cascade of tumor progression, such as epithelial-to-mesenchymal transition of carcinoma cells, tumor cell contact with the basement membrane, invasion into neighboring tissues as well as production and activation of ECM-degrading MMPs. Besides their direct involvement in tumor progression as cell surface molecules on tumor cells, integrins in normal cells surrounding a tumor, e.g. endothelial cells, can also determine various cancer characteristics, such as tumor-induced neoangiogenesis and immune resistance. Hence, integrins are relevant pharmacological targets in tumor biology. Spurred by the recent success to generate pharmaceutical mimetics of RGD-dependent integrins and by the integrins easy accessibility on the cell surface, the hope is rising that also RGD-independent integrins, such as the collagen- and laminin-binding integrins, can be pharmacologically manipulated to fight integrin-dependent functions of cancer cells, which are necessary and at least partially specific for their proliferation and progression
Export Options
About this article
Cite this article as:
Eble A. Johannes and Haier Jorg, Integrins in Cancer Treatment, Current Cancer Drug Targets 2006; 6 (2) . https://dx.doi.org/10.2174/156800906776056518
DOI https://dx.doi.org/10.2174/156800906776056518 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
-
Mitogenomics: Recognizing the Significance of Mitochondrial Genomic Variation for Personalized Medicine
Current Pharmacogenomics and Personalized Medicine Tyrosine Kinase Inhibitors for the Treatment of Chronic Myeloid Leukemia
Anti-Cancer Agents in Medicinal Chemistry Editorial
Current Medical Imaging The Involvement of ERCC2/XPD and ERCC6/CSB Wild Type Alleles in Protection Against Aging and Cancer
Current Aging Science Effect of Formulation Variables on the Preparation of Ibuprofen Loaded Polymeric Nanoparticles
Pharmaceutical Nanotechnology Patent Selections:
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Activation of B Cells by a Dendritic Cell-Targeted Oral Vaccine
Current Pharmaceutical Biotechnology Potential Therapeutic Targets for Steroid-Resistant Asthma
Current Drug Targets Therapeutic Drugs that Behave as Mechanism-Based Inhibitors of Cytochrome P450 3A4
Current Drug Metabolism Decreased Parathyroid Hormone Levels Despite Persistent Hypocalcemia in Patients with Kidney Failure Recovering from Septic Shock
Endocrine, Metabolic & Immune Disorders - Drug Targets Hereditary Breast Cancer in Sub-Saharan Africa
Current Women`s Health Reviews Modulation of Ornithine Decarboxylase Activity by Phenolics Based Structurally Related Compounds Synthesized on Steroidal and Non-Steroidal Skeleton and their Radical Scavenging Action
Current Bioactive Compounds Intervention in Probabilistic Gene Regulatory Networks
Current Bioinformatics Combating Hepatitis C Virus by Targeting MicroRNA-122 Using Locked Nucleic Acids
Current Gene Therapy Important Classes of Bioactive Alkaloids from Marine Ascidians: Structures, Isolation and Bioactivity
Current Topics in Medicinal Chemistry New Ferrocene Compounds as Selective Cyclooxygenase (COX-2) Inhibitors: Design, Synthesis, Cytotoxicity and Enzyme-inhibitory Activity
Anti-Cancer Agents in Medicinal Chemistry NSCLC Structure-activity Relationship (SAR) Study of Diisothiocyanates for Antiproliferative Activity on A549 Human Non-small Cell Lung Carcinoma (NSCLC)
Letters in Organic Chemistry A Study of Correlation between Anti-peroxidative Potential of Quercetin and Ascorbic Acid with Malondialdehyde by RP-HPLC
Current Chemical Biology Synthesis of Novel Pyridine Bearing Biologically Active Imidiazolyl, Pyrazolyl, Oxa/thiadiazolyl and Urea Derivatives as Promising Anticancer Agents
Current Organic Synthesis Surgical Management of Medullary Thyroid Carcinoma in Pediatric Age
Current Pediatric Reviews