Antimigratory and antimetastatic effect of heparin-derived 4-18 unit oligosaccharides in a preclinical human melanoma metastasis model.

2.50
Hdl Handle:
http://hdl.handle.net/10541/109309
Title:
Antimigratory and antimetastatic effect of heparin-derived 4-18 unit oligosaccharides in a preclinical human melanoma metastasis model.
Authors:
Kenessey, István; Simon, Erika; Futosi, Krisztina; Bereczky, Bíborka; Kiss, Andrea; Erdödi, Ferenc; Gallagher, John T; Tímár, József; Tóvári, József
Abstract:
Heparin and its derivatives have been shown to inhibit angiogenesis and metastasis formation. Accordingly, we investigated the effect of heparin fragments containing 4 to 22 monomers on human melanoma cell proliferation, migration and invasion in vitro as well as on the in vivo metastatic potential in a SCID mouse model. Only oligosaccharide dp18 had significant inhibitory effect on cell proliferation. In contrast, cell migration was inhibited by all oligosaccharides studied except dp8 and dp22. Anti-CD44v3 antibody stimulated cell migration and invasion, and this effect could be attenuated by oligosaccharides dp4 and dp18. These fragments also inhibited the catalytic activity of myosin light chain phosphatase as well. Moreover, oligosaccharides dp4 and dp18 reduced the number of lung colonies formed in SCID mice intravenously injected with human melanoma cells, while dp22 proved to be ineffective in this respect. These studies revealed that fragments of heparin have an antimigratory and antimetastatic potential. These fragments lack the haemostatic effect of heparin, suggesting that they are potential specific antimetastatic agents in anticancer therapy.
Affiliation:
Department of Tumor Progression, National Institute of Oncology, Budapest, Hungary.
Citation:
Antimigratory and antimetastatic effect of heparin-derived 4-18 unit oligosaccharides in a preclinical human melanoma metastasis model. 2009, 102 (6):1265-73 Thromb. Haemost.
Journal:
Thrombosis and Haemostasis
Issue Date:
Dec-2009
URI:
http://hdl.handle.net/10541/109309
DOI:
10.1160/TH09-01-0059
PubMed ID:
19967160
Type:
Article
Language:
en
ISSN:
0340-6245
Appears in Collections:
All Paterson Institute for Cancer Research; School of Cancer and Imaging Sciences

Full metadata record

DC FieldValue Language
dc.contributor.authorKenessey, Istvánen
dc.contributor.authorSimon, Erikaen
dc.contributor.authorFutosi, Krisztinaen
dc.contributor.authorBereczky, Bíborkaen
dc.contributor.authorKiss, Andreaen
dc.contributor.authorErdödi, Ferencen
dc.contributor.authorGallagher, John Ten
dc.contributor.authorTímár, Józsefen
dc.contributor.authorTóvári, Józsefen
dc.date.accessioned2010-08-09T16:02:49Z-
dc.date.available2010-08-09T16:02:49Z-
dc.date.issued2009-12-
dc.identifier.citationAntimigratory and antimetastatic effect of heparin-derived 4-18 unit oligosaccharides in a preclinical human melanoma metastasis model. 2009, 102 (6):1265-73 Thromb. Haemost.en
dc.identifier.issn0340-6245-
dc.identifier.pmid19967160-
dc.identifier.doi10.1160/TH09-01-0059-
dc.identifier.urihttp://hdl.handle.net/10541/109309-
dc.description.abstractHeparin and its derivatives have been shown to inhibit angiogenesis and metastasis formation. Accordingly, we investigated the effect of heparin fragments containing 4 to 22 monomers on human melanoma cell proliferation, migration and invasion in vitro as well as on the in vivo metastatic potential in a SCID mouse model. Only oligosaccharide dp18 had significant inhibitory effect on cell proliferation. In contrast, cell migration was inhibited by all oligosaccharides studied except dp8 and dp22. Anti-CD44v3 antibody stimulated cell migration and invasion, and this effect could be attenuated by oligosaccharides dp4 and dp18. These fragments also inhibited the catalytic activity of myosin light chain phosphatase as well. Moreover, oligosaccharides dp4 and dp18 reduced the number of lung colonies formed in SCID mice intravenously injected with human melanoma cells, while dp22 proved to be ineffective in this respect. These studies revealed that fragments of heparin have an antimigratory and antimetastatic potential. These fragments lack the haemostatic effect of heparin, suggesting that they are potential specific antimetastatic agents in anticancer therapy.en
dc.language.isoenen
dc.subjectAnticancerous Agentsen
dc.subjectTumour Cell Lineen
dc.subjectLung Canceren
dc.subjectCancer Invasivenessen
dc.subjectCancer Transplantationen
dc.subject.meshAnimals-
dc.subject.meshAntigens, CD44-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshCell Line, Tumor-
dc.subject.meshCell Movement-
dc.subject.meshHeparin, Low-Molecular-Weight-
dc.subject.meshHumans-
dc.subject.meshLung Neoplasms-
dc.subject.meshMelanoma, Experimental-
dc.subject.meshMice-
dc.subject.meshMice, SCID-
dc.subject.meshNeoplasm Invasiveness-
dc.subject.meshNeoplasm Transplantation-
dc.subject.meshOligosaccharides-
dc.subject.meshProtein Phosphatase 1-
dc.subject.meshTransplantation, Heterologous-
dc.titleAntimigratory and antimetastatic effect of heparin-derived 4-18 unit oligosaccharides in a preclinical human melanoma metastasis model.en
dc.typeArticleen
dc.contributor.departmentDepartment of Tumor Progression, National Institute of Oncology, Budapest, Hungary.en
dc.identifier.journalThrombosis and Haemostasisen

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