Heparin, heparan sulfate and heparanase in cancer: remedy for metastasis?
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.
Li
Jin-Ping
JP
Department of Medical Biochemistry and Microbiology, The Biomedical Center, Box 582, S 75123, Uppsala University, Uppsala, Sweden. jin-ping.li@imbim.uu.se
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D006493:Heparin / Q000096:biosynthesis / Q000502:physiology*; D019763:Heparin Lyase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology / Q000627:therapeutic use; D006497:Heparan Sulfate / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D013379:Substrate Specificity; D013927:Thrombosis / Q000097:blood / Q000517:prevention & control
D000925:Anticoagulants; D006493:Heparin; D019763:Heparin Lyase; D006495:Heparin, Low-Molecular-Weight; D006497:Heparan Sulfate