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A Low Molecular Weight Heparin Inhibits Experimental Metastasis in Mice Independently of the Endothelial Glycocalyx

BACKGROUND: Some low molecular weight heparins (LMWHs) prolong survival of cancer patients and inhibit experimental metastasis. The underlying mechanisms are still not clear but it has been suggested that LMWHs (at least in part) limit metastasis by preventing cancer cell-induced destruction of the...

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Detalles Bibliográficos
Autores principales: Van Sluis, Geerte L., Nieuwdorp, Max, Kamphuisen, Pieter W., van der Vlag, Johan, Van Noorden, Cornelis J. F., Spek, C. Arnold
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2888573/
https://www.ncbi.nlm.nih.gov/pubmed/20574516
http://dx.doi.org/10.1371/journal.pone.0011200
Descripción
Sumario:BACKGROUND: Some low molecular weight heparins (LMWHs) prolong survival of cancer patients and inhibit experimental metastasis. The underlying mechanisms are still not clear but it has been suggested that LMWHs (at least in part) limit metastasis by preventing cancer cell-induced destruction of the endothelial glycocalyx. METHODOLOGY/PRINCIPAL FINDINGS: To prove or refute this hypothesis, we determined the net effects of the endothelial glycocalyx in cancer cell extravasation and we assessed the anti-metastatic effect of a clinically used LMWH in the presence and absence of an intact endothelial glycocalyx. We show that both exogenous enzymatic degradation as well as endogenous genetic modification of the endothelial glycocalyx decreased pulmonary tumor formation in a murine experimental metastasis model. Moreover, LMWH administration significantly reduced the number of pulmonary tumor foci and thus experimental metastasis both in the presence or absence of an intact endothelial glycocalyx. CONCLUSIONS: In summary, this paper shows that the net effect of the endothelial glycocalyx enhances experimental metastasis and that a LMWH does not limit experimental metastasis by a process involving the endothelial glycocalyx.