Actions of heparin that may affect the malignant process

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Abstract
BACKGROUND Heparin has many actions that may affect the malignant process, especially metastasis. METHODS The author conducted an extensive review of the available medical literature about heparin activity that may apply to important factors involved in the malignant process. RESULTS Thrombin is generated by tumors, and the resultant fibrin formation impedes natural killer cell activity. Microthrombi arrest tumor cells in capillaries. Heparin prevents the formation of thrombin and neutralizes its activity. Angiogenesis has an important role in metastasis; heparin minimizes angiogenesis via the inhibition of vascular endothelial growth factor, tissue factor, and platelet activating factor. It decreases tumor cell adhesion to vascular endothelium as it inhibits selectin and chemokine actions, and it also decreases the replication and activity of some oncogenic viruses. Matrix metalloproteinases, serine proteases, and heparanases have an important role in metastasis. Heparin decreases their activation and limits their effects. It competitively inhibits tumor cell attachment to heparan sulfate proteoglycans. It blocks the oncogenic action of ornithine decarboxylase and enhances the antineoplastic effect of transforming growth factor‐β. Heparin inhibits activator protein‐1, which is the nuclear target of many oncogenic signal transduction pathways, and it potently inhibits casein kinase II, which has carcinogenic activity. Platelet‐derived growth factor, which has oncogenic effects, is also inhibited by heparin, as are reverse transcriptase, telomerase, and topoisomerase prooncogenic actions. CONCLUSIONS These various heparin actions justify clinical investigation of its possible beneficial effect on malignant disease. Cancer 1999;85:257–72. © 1999 American Cancer Society.

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