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

István Kenessey; Erika Simon; Krisztina Futosi; Bíborka Bereczky; Andrea Kiss; Ferenc Erdödi; John T. Gallagher; József Tímár; József Tóvári

doi:10.1160/TH09-01-0059

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 102(06): 1265-1273
DOI: 10.1160/TH09-01-0059

Cellular Proteolysis and Oncology

Schattauer GmbH

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

István Kenessey

¹Department of Tumor Progression, National Institute of Oncology, Budapest, Hungary

²2nd Department of Pathology, Semmelweis University, Budapest, Hungary

,

Erika Simon

¹Department of Tumor Progression, National Institute of Oncology, Budapest, Hungary

,

Krisztina Futosi

¹Department of Tumor Progression, National Institute of Oncology, Budapest, Hungary

,

Bíborka Bereczky

¹Department of Tumor Progression, National Institute of Oncology, Budapest, Hungary

,

Andrea Kiss

³Cell Biology and Signaling Research Group of the Hungarian Academy of Sciences, Department of Medical Chemistry, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary

,

Ferenc Erdödi

³Cell Biology and Signaling Research Group of the Hungarian Academy of Sciences, Department of Medical Chemistry, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary

,

John T. Gallagher

⁴School of Cancer and Imaging Sciences, Faculty of Medical and Health Sciences, University of Manchester, Paterson Institute for Cancer Research, Manchester, UK

,

József Tímár

¹Department of Tumor Progression, National Institute of Oncology, Budapest, Hungary

²2nd Department of Pathology, Semmelweis University, Budapest, Hungary

,

József Tóvári

¹Department of Tumor Progression, National Institute of Oncology, Budapest, Hungary

⁵Department of Tumor Biology, National Korányi Institute of Pulmonology, Budapest, Hungary

› Author Affiliations

Abstract

Summary

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.

Keywords

Melanoma - oligosaccharides - cell - migration - xenograft - metastasis model

Full Text

References

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