Abstract
Heparanase is the unique and specific functional endoglycosidase capable of cleaving heparan sulfate (HS) chains. It exerts its enzymatic activity catalyzing the cleavage of the β (1,4)-glycosidic bond between glucuronic acid and glucosamine residue. HS cleavage results in remodelling of the extracellular matrix as well as in regulating the release of many HS-linked molecules such as growth factors, cytokines and enzymes involved in inflammation, wound healing and tumour invasion. A pro-metastatic and pro-angiogenic role for this enzyme has been widely demonstrated in many primary human tumours since high levels of heparanase correlate with lymph node and distant metastasis, elevated micro vessel density and reduced survival of cancer patients. Recently, data have been reported that heparanase regulates heparan sulfate proteoglycan syndecan-1 and promotes its shedding from the cell surface. Shed syndecan-1 in turn controls tumour growth, metastasis and neo-angiogenesis mainly by promoting growth-factor signaling in the tumour milieu. Considering that, once inactivated, there are no other molecules capable of performing the same function, it is evident how this enzyme may be an effective and attractive drug target. Several heparanase inhibitors have been developed and some of them have undergone clinical trials showing efficacy against tumours. In this mini-review we will discuss current knowledge of heparanase involvement in cancer as well as its targeted inhibition as a promising therapeutic option in tumour treatment.
Keywords: Angiogenesis, cancer, extracellular matrix, heparanase, heparanase inhibitors, heparan sulfate, metastasis.
Current Cancer Drug Targets
Title:Heparanase as a Target in Cancer Therapy
Volume: 14 Issue: 3
Author(s): Valentina Masola, Maria Francesca Secchi, Giovanni Gambaro and Maurizio Onisto
Affiliation:
Keywords: Angiogenesis, cancer, extracellular matrix, heparanase, heparanase inhibitors, heparan sulfate, metastasis.
Abstract: Heparanase is the unique and specific functional endoglycosidase capable of cleaving heparan sulfate (HS) chains. It exerts its enzymatic activity catalyzing the cleavage of the β (1,4)-glycosidic bond between glucuronic acid and glucosamine residue. HS cleavage results in remodelling of the extracellular matrix as well as in regulating the release of many HS-linked molecules such as growth factors, cytokines and enzymes involved in inflammation, wound healing and tumour invasion. A pro-metastatic and pro-angiogenic role for this enzyme has been widely demonstrated in many primary human tumours since high levels of heparanase correlate with lymph node and distant metastasis, elevated micro vessel density and reduced survival of cancer patients. Recently, data have been reported that heparanase regulates heparan sulfate proteoglycan syndecan-1 and promotes its shedding from the cell surface. Shed syndecan-1 in turn controls tumour growth, metastasis and neo-angiogenesis mainly by promoting growth-factor signaling in the tumour milieu. Considering that, once inactivated, there are no other molecules capable of performing the same function, it is evident how this enzyme may be an effective and attractive drug target. Several heparanase inhibitors have been developed and some of them have undergone clinical trials showing efficacy against tumours. In this mini-review we will discuss current knowledge of heparanase involvement in cancer as well as its targeted inhibition as a promising therapeutic option in tumour treatment.
Export Options
About this article
Cite this article as:
Masola Valentina, Secchi Francesca Maria, Gambaro Giovanni and Onisto Maurizio, Heparanase as a Target in Cancer Therapy, Current Cancer Drug Targets 2014; 14 (3) . https://dx.doi.org/10.2174/1568009614666140224155124
DOI https://dx.doi.org/10.2174/1568009614666140224155124 |
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
-
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 Human Carcinogenesis and Bracken Fern: A Review of the Evidence
Current Medicinal Chemistry Thirty Years of Polyamine-Related Approaches to Cancer Therapy. Retrospect and Prospect. Part 1. Selective Enzyme Inhibitors
Current Drug Targets Zebrafish Model in Drug Safety Assessment
Current Pharmaceutical Design Possibilities of Poly(D,L-lactide-co-glycolide) in the Formulation of Nanomedicines Against Cancer
Current Drug Targets The Production and Role of Gastrin-17 and Gastrin-17-Gly in Gastrointestinal Cancers
Protein & Peptide Letters Potential Therapeutic Targets of Curcumin, Most Abundant Active Compound of Turmeric Spice: Role in the Management of Various Types of Cancer
Recent Patents on Anti-Cancer Drug Discovery Organoselenium Compounds in Cancer Chemoprevention
Mini-Reviews in Medicinal Chemistry Zoledronic Acid -a Multiplicity of Anti-Cancer Action
Current Medicinal Chemistry Target Driven Preclinical Screening for New Antimitotic Chemotherapy Agents
Current Topics in Medicinal Chemistry Small Heat Shock Proteins and the Endoplasmic Reticulum: Potential Attractive Therapeutic Targets?
Current Molecular Medicine Computational Analysis of miRNA and their Gene Targets Significantly Involved in Colorectal Cancer Progression
MicroRNA The Correlation between EGFR and Androgen Receptor Pathways: A Novel Potential Prognostic Marker in Gastric Cancer
Anti-Cancer Agents in Medicinal Chemistry Role of the Akt Pathway in Prostate Cancer
Current Cancer Drug Targets Neonatal Germ Cell Tumors
Current Pediatric Reviews Application of Bioactive Compounds and Drugs to Target Epigenetic Enzymes and Non-coding RNAs, Exploiting New Delivery Systems for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Adipocyte Fatty Acid Binding Protein (A-FABP) as a Potential New Therapeutic Target for the Treatment of Obesity - Associated Cancers
Current Drug Targets Lanthanum, Gallium and their Impact on Oxidative Stress
Current Medicinal Chemistry Extracellular HSP90: An Emerging Target for Cancer Therapy
Current Signal Transduction Therapy Mechanisms of Action of DNA-Damaging Anticancer Drugs in Treatment of Carcinomas: Is Acute Apoptosis an “Off-Target” Effect?
Mini-Reviews in Medicinal Chemistry