Abstract
Malignant tumor cells invade normal tissues in the vicinity of cancer through devastating the extracelluar matrix and blood vessel wall of the tissues. An important step in this process is degradation of heparan sulfate proteoglycan, a carbohydrate-protein complex. Heparan sulfate proteoglycan is a major component of the extracellular matrix, and is essential for the self-assembly, insolubility and barrier properties of basement membranes. Heparanase is an endoglucuronidase that cleaves heparan sulfate and expression level of this enzyme correlates with metastatic potential of tumor cells. Treatment with heparanase inhibitors markedly reduces the incidence of metastasis in experimental animals. Heparin, a widely used anticoagulant, is structurally related to heparan sulfate and a natural substrate of heparanase. Long-term treatment of cancer patients having venous thromboembolism with low molecular weight heparin showed improved survival rate. Understanding the functional roles and the corresponding molecular mechanisms of heparin, heparan sulfate and heparanase in cancer development may pave the way for exploring remedies against tumor metastasis.
Keywords: Heparin, heparan sulfate, heparanase, tumor metastasis, angiogenesis, extracellular matrix, inhibitor, proteoglycan
Anti-Cancer Agents in Medicinal Chemistry
Title: Heparin, Heparan Sulfate and Heparanase in Cancer: Remedy for Metastasis?
Volume: 8 Issue: 1
Author(s): Jin-Ping Li
Affiliation:
Keywords: Heparin, heparan sulfate, heparanase, tumor metastasis, angiogenesis, extracellular matrix, inhibitor, proteoglycan
Abstract: Malignant tumor cells invade normal tissues in the vicinity of cancer through devastating the extracelluar matrix and blood vessel wall of the tissues. An important step in this process is degradation of heparan sulfate proteoglycan, a carbohydrate-protein complex. Heparan sulfate proteoglycan is a major component of the extracellular matrix, and is essential for the self-assembly, insolubility and barrier properties of basement membranes. Heparanase is an endoglucuronidase that cleaves heparan sulfate and expression level of this enzyme correlates with metastatic potential of tumor cells. Treatment with heparanase inhibitors markedly reduces the incidence of metastasis in experimental animals. Heparin, a widely used anticoagulant, is structurally related to heparan sulfate and a natural substrate of heparanase. Long-term treatment of cancer patients having venous thromboembolism with low molecular weight heparin showed improved survival rate. Understanding the functional roles and the corresponding molecular mechanisms of heparin, heparan sulfate and heparanase in cancer development may pave the way for exploring remedies against tumor metastasis.
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Cite this article as:
Li Jin-Ping, Heparin, Heparan Sulfate and Heparanase in Cancer: Remedy for Metastasis?, Anti-Cancer Agents in Medicinal Chemistry 2008; 8 (1) . https://dx.doi.org/10.2174/187152008783330824
DOI https://dx.doi.org/10.2174/187152008783330824 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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