Antisense-mediated Suppression of Heparanase Gene Inhibits Melanoma Cell Invasion

Overview

Journal Neoplasia

Publisher Elsevier

Specialty Oncology

Date 2005 Apr 1

PMID 15799825

Citations 23

Authors

Madhuchhanda Roy

Jane Reiland

Brian P Murry

Vladimir Chouljenko

Konstantin G Kousoulas

Dario Marchetti

Affiliations

Soon will be listed here.

Abstract

Cancer metastasis, is a frequent manifestation of malignant melanoma progression. Successful invasion into distant organs by tumor cells must include attachment to microvessel endothelial cells, and degradation of basement membranes and extracellular matrix (ECM). Heparan sulfate proteoglycans (HSPG) are essential and ubiquitous macromolecules associated with the cell surface and ECM of a wide range of cells and tissues. Heparanase (HPSE-1) is an ECM degradative enzyme, which degrades the heparan sulfate (HS) chains of HSPG at specific intrachain sites. To investigate effects of changes in heparanase gene expression in metastatic melanoma cells, we constructed adenoviral vectors containing the full-length human HPSE-1 cDNA in both sense (Ad-S/hep) and antisense orientations (Ad-AS/hep). We found increased HPSE-1 expression and activity in melanoma cell lines following Ad-S/hep infection by Western blot analyses and specific HPSE-1 activity assay. Conversely, HPSE-1 content was significantly inhibited following infection with Ad-AS/Hep. Importantly, HPSE-1 modulation by these adenoviral constructs correlated with invasive cellular properties in vitro and in vivo. Our results suggest that HPSE-1 not only contributes to the invasive phenotype of melanoma cells, but also that the Ad-AS/hep-mediated inhibition of its enzymatic activity can be efficacious in the prevention and treatment of melanoma metastasis.

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References

Iozzo R . Heparan sulfate proteoglycans: intricate molecules with intriguing functions. J Clin Invest. 2001; 108(2):165-7. PMC: 203034. DOI: 10.1172/JCI13560. View

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

Ishikawa M, Dennis J, Man S, Kerbel R . Isolation and characterization of spontaneous wheat germ agglutinin-resistant human melanoma mutants displaying remarkably different metastatic profiles in nude mice. Cancer Res. 1988; 48(3):665-70. View

Sasaki N, Higashi N, Taka T, Nakajima M, Irimura T . Cell surface localization of heparanase on macrophages regulates degradation of extracellular matrix heparan sulfate. J Immunol. 2004; 172(6):3830-5. DOI: 10.4049/jimmunol.172.6.3830. View

Marchetti D . Specific degradation of subendothelial matrix proteoglycans by brain-metastatic melanoma and brain endothelial cell heparanases. J Cell Physiol. 1997; 172(3):334-42. DOI: 10.1002/(SICI)1097-4652(199709)172:3<334::AID-JCP7>3.0.CO;2-P. View

Marchetti D, Denkins Y, Reiland J, Greiter-Wilke A, Galjour J, Murry B . Brain-metastatic melanoma: a neurotrophic perspective. Pathol Oncol Res. 2003; 9(3):147-58. DOI: 10.1007/BF03033729. View

Hulett M, Freeman C, Hamdorf B, Baker R, Harris M, Parish C . Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis. Nat Med. 1999; 5(7):803-9. DOI: 10.1038/10525. View

Sanderson R . Heparan sulfate proteoglycans in invasion and metastasis. Semin Cell Dev Biol. 2001; 12(2):89-98. DOI: 10.1006/scdb.2000.0241. View

Kjellen L, Lindahl U . Proteoglycans: structures and interactions. Annu Rev Biochem. 1991; 60:443-75. DOI: 10.1146/annurev.bi.60.070191.002303. View

10.

Liu D, Shriver Z, Venkataraman G, El Shabrawi Y, Sasisekharan R . Tumor cell surface heparan sulfate as cryptic promoters or inhibitors of tumor growth and metastasis. Proc Natl Acad Sci U S A. 2002; 99(2):568-73. PMC: 117346. DOI: 10.1073/pnas.012578299. View

11.

Kelly T, Miao H, Yang Y, Navarro E, Kussie P, Huang Y . High heparanase activity in multiple myeloma is associated with elevated microvessel density. Cancer Res. 2003; 63(24):8749-56. View

12.

Nakajima M, Irimura T, Nicolson G . Heparanases and tumor metastasis. J Cell Biochem. 1988; 36(2):157-67. DOI: 10.1002/jcb.240360207. View

13.

Vlodavsky I, Friedmann Y . Molecular properties and involvement of heparanase in cancer metastasis and angiogenesis. J Clin Invest. 2001; 108(3):341-7. PMC: 209369. DOI: 10.1172/JCI13662. View

14.

Simizu S, Ishida K, Wierzba M, Osada H . Secretion of heparanase protein is regulated by glycosylation in human tumor cell lines. J Biol Chem. 2003; 279(4):2697-703. DOI: 10.1074/jbc.M300541200. View

15.

Miao H, Elkin M, Aingorn E, Stein C, Vlodavsky I . Inhibition of heparanase activity and tumor metastasis by laminarin sulfate and synthetic phosphorothioate oligodeoxynucleotides. Int J Cancer. 1999; 83(3):424-31. DOI: 10.1002/(sici)1097-0215(19991029)83:3<424::aid-ijc20>3.0.co;2-l. View

16.

Iozzo R, Cohen I, Grassel S, Murdoch A . The biology of perlecan: the multifaceted heparan sulphate proteoglycan of basement membranes and pericellular matrices. Biochem J. 1994; 302 ( Pt 3):625-39. PMC: 1137278. DOI: 10.1042/bj3020625. View

17.

Folkman J . Angiogenesis-dependent diseases. Semin Oncol. 2001; 28(6):536-42. DOI: 10.1016/s0093-7754(01)90021-1. View

18.

Bernfield M, Gotte M, Park P, Reizes O, Fitzgerald M, Lincecum J . Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem. 2000; 68:729-77. DOI: 10.1146/annurev.biochem.68.1.729. View

19.

Parish C, Coombe D, JAKOBSEN K, BENNETT F, Underwood P . Evidence that sulphated polysaccharides inhibit tumour metastasis by blocking tumour-cell-derived heparanases. Int J Cancer. 1987; 40(4):511-8. DOI: 10.1002/ijc.2910400414. View

20.

Ernst S, Venkataraman G, Winkler S, Godavarti R, Langer R, Cooney C . Expression in Escherichia coli, purification and characterization of heparinase I from Flavobacterium heparinum. Biochem J. 1996; 315 ( Pt 2):589-97. PMC: 1217237. DOI: 10.1042/bj3150589. View