Heparanase and Its Applications in Cancer Therapy

Abstract

Abstract: Heparanase（Hpa）is the only endo-glycosidase which cleaves heparan sulfate（HS）in mammalian. The enzyme also can disrupt the integrity of the extracellular matrix（ECM）and basement membrane（BM）, to release various growth factors from the ECM. Hpa is associated with migration and invasion of cancer cells. Recently, a series of studies have indicated that Hpa was expressed in most advanced cancers, especially in malignant cancer, while decreased expression of Hpa is helpful to inhibit the migration of cancer cells. Heparanase can be used as a potential therapeutic target for cancers. This paper reviews the structure and functions of Hpa, its role in promoting cancer metastasis and the application in cancer therapy.

Key words: Heparanase, Cancer migration, Cancer therapy

Wang Jing, Chao Getu, Li Bei, Wang Zhigang. Heparanase and Its Applications in Cancer Therapy[J]. Biotechnology Bulletin, 2014, 0(6): 57-61.

References

[1] Kjellen L, Lindahl U. Proteoglycans：structures and interactions[J] . Annu Rev Biochem, 1991, 60：443-475.
[2] Iozzo RV. Matrix proteoglycans：from molecular design to cellular function[J] . Annu Rev Biochem, 1998, 67：609-652.
[3] Capila I, Linhardt RJ. Heparin-protein interactions[J] . Angew Chem Int Ed Engl, 2002, 41：391-412.
[4] Lindahl U, Li JP. Interactions between heparan sulfate and proteins-design and functional implications[J] . Int Rev Cell Mol Biol, 2009, 276：105-159.
[5] Vlodavsky I, Friedmann Y. Molecular properties and involvement of heparanase in cancer metastasis and angiogenesis[J] . J Clin Invest, 2001, 108：341-347.
[6] Gray E, Mulloy B, Barrowcliffe TW. Heparin and low molecular-weight heparin[J] . Thromb Haemost, 2008, 99：807-818.
[7] Lindahl U. Heparan sulfate-protein interactions-a concept for drug design[J] . Thromb Haemost, 2007, 98：109-115.
[8] Voldavsky I, Friedmann Y, Elkin M, et al. Cloning of heparanase：gene cloning, expression and function in tumor progression and metastasis[J] . Nat Med, 1999, 5：793.
[9] Xu X, Ding J, Rao G, et al. Estradiol induces heparanase-1 expression and heparan sulphate proteoglycan degradation in human endome-trium[J] . Hum Reprod, 2007, 22：927-937.
[10] Fux L, Ilan N, Sanderson RD, et al. Heparanase：busy at the cell surface[J] . Trends Biochem Sci, 2009, 34：511-519.
[11] Vreys V, David G. Mammalian heparanase：what is the message? [J] . Cell Mol Med, 2007, 11：427-452.
[12] Vlodavsky I, Beckhove P, Lerner I, et al. Significance of heparanase in cancer and inflammation[J] . Cancer Microenviron, 2012, 5：115-132.
[13] Lazo-Langner A, Goss GD, Spaans JN, et al. The effect of low-mole-cular-weight heparin on cancer survival[J] . Thromb Haemost, 2007, 5：729-737.
[14] Lerner I, Baraz L, Pikarsky E, et al. Function of heparanase in prostate tumorigenesis：potential for therapy[J] . Clin Cancer Res, 2008, 14：668-676.
[15] Doweck I, Kaplan-Cohen V, Naroditsky I, et al. Heparanase localization and expression by head and neck cancer：correlation with tumor progression and patient surrival[J] . Neoplasia, 2006, 8：1055-1061.
[16] Nobuhisia T, Naomoto Y, Ohkawa T, et al. Heparanase expression correlates with malignant potential in human colon cancer[J] . Cancer Res Clin Oncol, 2005, 131：229-237.
[17] Raman K, Karuturi R, Swarup VP, et al. Discovery of novel sulfon-ated small molecules that inhibit vascular tube formation[J] . Bioorganic & Medicinal Chemistry Letters, 2012, 22：4467-4470.
[18] Ilan N, Elkin M, Vlodavsky I. Regulation, function and clinical significance of heparanase in cancer metastasis and angiogenesis [J] . Int J Biochem Cell Biol, 2006, 38：2018-2039.
[19] Borsig L, Wong R, Feramisco J, et al. Heparin and cancer revisited： mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis[J] . Proc Natl Acad Sci USA, 2001, 98：3335-3357.
[20] Dredge K, Hammond E, Handley P, et al. PG545, a dual heparanase and angiogenesis inhibitor, induces potent anti-tumour and anti-metastatic efficacy in preclinical models[J] . British Journal of Cancer, 2011, 104：635-642.
[21] Hammond E, Brandt R, Dredge K. PG545, a heparan sulfate mimetic, reduces heparanase expression in vivo, blocks spontaneous metastases and enhances overall survival in the 4T1 breast carcin-oma model[J] . PLoS One, 2012, 7：1-11.
[22] Dredge K, Hammond E, Davis K, et al. The PG500 series：novel heparan sulfate mimetics as potent angiogenesis and heparanase inhibitors for cancer therapy[J] . Invest New Drugs, 2010, 28：276-283.
[23] Levy-Adam F, Abboud-Jarrous G, Guerrini M, et al. Identification and characterization of heparin /heparan sulfate binding domains of the endoglycosidase heparanase[J] . J Biol Chem, 2005, 280：20457-20466.
[24] Zetser A, Levy-Adam F, Kaplan V, et al. Processing and activation of latent heparanase occurs in lysosomes[J] . J Cell Sci, 2004, 117：2249-2258.
[25] Marchetti D, Reiland J, Erwin B, et al. Inhibition of heparanase activity and heparanase-induced angiogenesis by suramin analogues[J] . Int J Cancer, 2003, 104：167-174.
[26] Miao HQ, Elkin M, Aingorn E, et al. Inhibition of heparanase activity and tumor metastasis by laminarin sulfate and synthetic phosphorothioate oligo deoxynucleo tides[J] . Int J Cancer, 1999, 83：424-431.
[27] Liu XY, Tang QS, Chen HC, et al. Lentiviral miR30-based RNA interference against heparanase suppresses melanoma metastasis with lower liver and lung toxicity[J] . Int J Bio Sci, 2013, 9：564-577.