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 endothelial glycocalyx.


RESULTS
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.
Van Sluis
Geerte L
GL
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Nieuwdorp
Max
M
Kamphuisen
Pieter W
PW
van der Vlag
Johan
J
Van Noorden
Cornelis J F
CJ
Spek
C Arnold
CA
D000818:Animals; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000473:pathology*; D019276:Glycocalyx / Q000378:metabolism*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000473:pathology*; D009374:Neoplasms, Experimental
D006495:Heparin, Low-Molecular-Weight