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Anti-Metastatic Activities of Heparins

Author(s): Marian Simka | Tomasz Urbanek

Journal: Journal of Cancer Molecules
ISSN 1816-0735

Volume: 5;
Issue: 1;
Start page: 3;
Date: 2009;
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Keywords: heparin | selectin | CXCL12 | CXCR4 | heparanase | metastasis

Heparins are commonly administered to cancer patients for the treatment and prophylaxis of thromboembolic events. Importantly, apart from the anti-thrombotic action of these drugs, several clinical trials have demonstrated an improved survival of cancer patients who were administered low-molecular-weight heparins (LMWHs). This improved survival was independent of the anti-thrombotic efficacy, since vitamin K antagonists did not improve clinical prognosis. Moreover, this protective effect was not the result of an inhibition of the growth of primary tumors, but rather the prevention of the spreading of cancer through metastases. This has been also shown in some animal experiments. The protective effect of heparins, however, could be seen only for some kinds of cancer. This review presents the most likely mechanisms by which heparins and heparin derivatives attenuate cancer metastases. Most likely, heparin-dependent inhibition of metastases could be secondary to a restraint of P- and L-selectin-mediated interactions of platelets with circulating neoplastic cells, a modulation of the chemokine CXCL12/CXCR4 axis, an inhibition of heparanase activity, or the inhibition of angiogenesis in the tumor. The combined effect of the above-described mechanisms should be also taken into account. This potential anti-metastatic role of heparins may imply that cancer patients should be administered LMWHs instead of oral anticoagulants for the prevention and treatment of thromboembolic events. Clinical recommendations on LMWHs in cancer patients should be revisited in regards to the anti-metastatic efficacy of these drugs. Additionally, findings regarding heparins may provide a useful framework for research on novel anti-metastatic drugs.
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