Clexane Attenuates Metastasis by Inhibition of Heparanase Activity and Function

There is a compelling evidence for the clinical relevance of heparanase, making heparanase as an attractive target for the development of anti-cancer drug. Heparanase is an endoglycosidase that degrades the heparan sulfate (HS) of extracellular matrix inducing structural alterations of the extracellular matrix (ECM). Heparanase expression shows a direct correlation with the aggressiveness of the HCC cancer disease and well correlates with the overall survival of transplanted and resected patients. Low-molecular weight heparin (LMWH) is the mostly clinically used anticoagulant/antithrombotic drug, and has recently been shown to exhibit anti-metastatic activity. (LMWH) was showed to reduce metastasis in many murine models according to multiple mechanisms. The mechanism exerted by (LMWH) on heparanase promoting tumor progression still not well investigated. The aim of the present study was to determine the capacity of clexane a (LMWH) to inhibit heparanase and to test their potential to effects on metastasis and inflammation in tow experimental mice models. Clexane effectively attenuated metastasis of MC38-Luc carcinoma but no effect was observed on metastasis of B16F10Luc2 melanoma cells. Our study supports the ability of clexane to inhibit heparanase activity and contributes to attenuate metastasis in hepatic cancer. The reduction of metastasis by a daily treatment with clexane strongly suggests that (LMWH) primarily reduces metastatic disease by inhibiting heparanase fuction and activity. However, such (LMWH) could have further effects at higher doses.