Antimetastatic activities of heparins and modified heparins. Experimental evidence

Abstract

Heparin is commonly used for prevention or treatment of cancer-associated thromboembolism. Recent clinical evidence indicates that heparin, and low-molecular weight heparin improves survival of cancer patients. Experimental evidence from various animal models consistently supports the ability of heparin to attenuate metastasis. Heparin, apart from its anticoagulant activity contains a variety of biological activities possibly affecting cancer progression, including: inhibition of heparanase, blocking of P-and L-selectin mediated cell adhesion, and inhibition of angiogenesis. The delineation of antimetastatic activity of heparin is in the focus of several ongoing investigations. This review summarizes the current experimental evidence on the biology of heparin as a potential treatment cancer progression. 3

Old and new applications of non-anticoagulant heparin

“…A recent report indicated an additional chemo-sensitizing activity of heparin through inhibition of P-glycoprotein-mediated multidrug resistance [31]. The results of "in vitro", "in vivo" studies and clinical trials have been reviewed [29,[32][33][34]. Retrospective evaluation of early clinical trials indicated that heparin can provide survival benefits to cancer patients compared to other anti-thrombotics [32].…”

Heparin-Like Drugs with Antiangiogenic Activity

“…heparanase) and formation of the capillary vessel lumen (Marchetti et al, 2008). Moreover, tissue factor (TF) and its natural inhibitor (TFPI) are also important heparin-binding proteins that perform well-recognized roles in the regulation of angiogenesis, tumor growth and metastasis (Bobek & Kobarik, 2004;Borsig, 2010;Debergh et al, 2010;Norrby, 2006). LMWH may influence angiogenesis through modulation of the expression of angiogenic growth factors (VEGF and bFGF) and their inhibitors (Dogan et al, 2011;Gasowska et al, 2009;Mousa & Petersen, 2009).…”

The Role of Adhesion Receptors in Melanoma Metastasis and Therapeutic Intervention Thereof

“…Several molecular mechanisms exist to explain the antimetastatic efficiency of heparin. The reader is referred to excellent reviews in this field (Borsig, 2010;Casu et al 2008) from which the inhibitory capacity of heparin towards P-and L-selectin binding should be highlighted here. Heparin as a highly sulfated, acidic polysaccharide has the ability to compete with the natural mucin-like selectin ligands.…”