Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
PLoS One. 2010 Jun 21;5(6):e11200. doi: 10.1371/journal.pone.0011200.
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.
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.
一些低分子量肝素（LMWHs）延长了癌症患者的生存时间，并抑制了实验性转移。其潜在机制尚不清楚，但有人认为，LMWHs（至少部分）通过防止癌细胞诱导的内皮糖萼破坏来限制转移。
方法/主要发现：为了证明或反驳这一假设，我们确定了内皮糖萼在癌细胞渗出中的净效应，并在存在和不存在完整内皮糖萼的情况下评估了一种临床使用的 LMWH 的抗转移作用。我们发现，外源性酶降解以及内皮糖萼的内源性基因修饰均降低了小鼠实验性转移模型中的肺肿瘤形成。此外，LMWH 给药显著减少了肺肿瘤灶的数量，从而减少了实验性转移，无论是在存在还是不存在完整的内皮糖萼的情况下。
总之，本文表明内皮糖萼的净效应增强了实验性转移，而 LMWH 并不通过涉及内皮糖萼的过程来限制实验性转移。
