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

I. Kenessey, Erika Simon, Krisztina Futosi, Bíborka Bereczky, A. Kiss, F. Erdődi, John T. Gallagher, J. Tímár, J. Tóvári

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1265-1273
Number of pages9
JournalThrombosis and Haemostasis
Volume102
Issue number6
DOIs
Publication statusPublished - Dec 2009

Fingerprint

Oligosaccharides
Heparin
Melanoma
Neoplasm Metastasis
Cell Movement
SCID Mice
Myosin-Light-Chain Phosphatase
Cell Proliferation
Hemostatics
Antineoplastic Agents
Anti-Idiotypic Antibodies
Lung
Therapeutics

Keywords

  • Cell migration
  • Melanoma
  • Metastasis model
  • Oligosaccharides
  • Xenograft

ASJC Scopus subject areas

  • Hematology

Cite this

Antimigratory and antimetastatic effect of heparin-derived 4-18 unit oligosaccharides in a preclinical human melanoma metastasis model. / Kenessey, I.; Simon, Erika; Futosi, Krisztina; Bereczky, Bíborka; Kiss, A.; Erdődi, F.; Gallagher, John T.; Tímár, J.; Tóvári, J.

In: Thrombosis and Haemostasis, Vol. 102, No. 6, 12.2009, p. 1265-1273.

Research output: Contribution to journalArticle

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AU - Kiss, A.

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AU - Gallagher, John T.

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