Antisense-Mediated Suppression of Heparanase Gene Inhibits Melanoma Cell Invasion
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, degradation of basement membranes and extracellular matrix (ECM). Heparan sulfate proteoglycans (HSPG) are...
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| Format: | Article |
| Language: | English |
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Elsevier
2005-03-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558605800260 |
| _version_ | 1828757190884720640 |
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| author | Madhuchhanda Roy Jane Reiland Brian P. Murry Vladimir Chouljenko Konstantin G. Kousoulas Dario Marchetti |
| author_facet | Madhuchhanda Roy Jane Reiland Brian P. Murry Vladimir Chouljenko Konstantin G. Kousoulas Dario Marchetti |
| author_sort | Madhuchhanda Roy |
| collection | DOAJ |
| description | 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, 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 fulllength 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. |
| first_indexed | 2024-12-11T00:23:25Z |
| format | Article |
| id | doaj.art-7bb62b425bd0453ca0eb67934fe01e85 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-11T00:23:25Z |
| publishDate | 2005-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-7bb62b425bd0453ca0eb67934fe01e852022-12-22T01:27:39ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022005-03-017325326210.1593/neo.04493Antisense-Mediated Suppression of Heparanase Gene Inhibits Melanoma Cell InvasionMadhuchhanda Roy0Jane Reiland1Brian P. Murry2Vladimir Chouljenko3Konstantin G. Kousoulas4Dario Marchetti5Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University at Baton Rouge, Baton Rouge, LA 70803, USADepartment of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University at Baton Rouge, Baton Rouge, LA 70803, USADepartment of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University at Baton Rouge, Baton Rouge, LA 70803, USADivision of Biotechnology and Molecular Medicine, School of Veterinary Medicine, Louisiana State University at Baton Rouge, Baton Rouge, LA 70803, USADivision of Biotechnology and Molecular Medicine, School of Veterinary Medicine, Louisiana State University at Baton Rouge, Baton Rouge, LA 70803, USADepartment of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University at Baton Rouge, Baton Rouge, LA 70803, USACancer metastasis is a frequent manifestation of malignant melanoma progression. Successful invasion into distant organs by tumor cells must include attachment to microvessel endothelial cells, 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 fulllength 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.http://www.sciencedirect.com/science/article/pii/S1476558605800260Malignant melanomaheparanaseheparan sulfateinvasion and metastasisanti-sense gene delivery |
| spellingShingle | Madhuchhanda Roy Jane Reiland Brian P. Murry Vladimir Chouljenko Konstantin G. Kousoulas Dario Marchetti Antisense-Mediated Suppression of Heparanase Gene Inhibits Melanoma Cell Invasion Neoplasia: An International Journal for Oncology Research Malignant melanoma heparanase heparan sulfate invasion and metastasis anti-sense gene delivery |
| title | Antisense-Mediated Suppression of Heparanase Gene Inhibits Melanoma Cell Invasion |
| title_full | Antisense-Mediated Suppression of Heparanase Gene Inhibits Melanoma Cell Invasion |
| title_fullStr | Antisense-Mediated Suppression of Heparanase Gene Inhibits Melanoma Cell Invasion |
| title_full_unstemmed | Antisense-Mediated Suppression of Heparanase Gene Inhibits Melanoma Cell Invasion |
| title_short | Antisense-Mediated Suppression of Heparanase Gene Inhibits Melanoma Cell Invasion |
| title_sort | antisense mediated suppression of heparanase gene inhibits melanoma cell invasion |
| topic | Malignant melanoma heparanase heparan sulfate invasion and metastasis anti-sense gene delivery |
| url | http://www.sciencedirect.com/science/article/pii/S1476558605800260 |
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