Cancer cell adhesion and metastasis: selectins, integrins, and the inhibitory potential of heparins - PubMed (original) (raw)

Cancer cell adhesion and metastasis: selectins, integrins, and the inhibitory potential of heparins

Gerd Bendas et al. Int J Cell Biol. 2012.

Abstract

Cell adhesion molecules play a significant role in cancer progression and metastasis. Cell-cell interactions of cancer cells with endothelium determine the metastatic spread. In addition, direct tumor cell interactions with platelets, leukocytes, and soluble components significantly contribute to cancer cell adhesion, extravasation, and the establishment of metastatic lesions. Clinical evidence indicates that heparin, commonly used for treatment of thromboembolic events in cancer patients, is beneficial for their survival. Preclinical studies confirm that heparin possesses antimetastatic activities that lead to attenuation of metastasis in various animal models. Heparin contains several biological activities that may affect several steps in metastatic cascade. Here we focus on the role of cellular adhesion receptors in the metastatic cascade and discuss evidence for heparin as an inhibitor of cell adhesion. While P- and L-selectin facilitation of cellular contacts during hematogenous metastasis is being accepted as a potential target of heparin, here we propose that heparin may also interfere with integrin activity and thereby affect cancer progression. This review summarizes recent findings about potential mechanisms of tumor cell interactions in the vasculature and antimetastatic activities of heparin.

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Figures

Figure 1

Figure 1

Selectins and integrins contribute to metastatic spread. (a) Schematic presentation of selectin- and integrin-mediated cancer cell interactions with several blood constituents (e.g., platelets, leukocytes, and endothelial cells) during hematogenous metastasis. (b) Heparin application in mouse models blocks both P- and L-selectin-mediated; and VLA4-mediated interactions of cancer cells within blood circulation thereby affecting metastasis.

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