Cancer metastasis is a highly coordinated and dynamic multistep process in which cancer cells interact with a variety of host cells. Morphological studies have documented the association of circulating tumor cells with host platelets. Tumor cell-induced platelet aggregation (TCIPA) contributes significantly to hematogenous metastasis; however, the molecular mechanisms involved in breast cancer TCIPA are poorly characterized. In this study, MCF-7 metastatic human breast cancer cells induced dose-dependent aggregation of washed platelets. Four major platelet activation pathways, glycoprotein (GP)-Ib-IX, GPIIb/IIIa, thromboxane (TX)-A2 and adenosine diphosphate (ADP) were activated during TCIPA and were inhibited by their respective inhibitors, 7E3, SZ-1, aspirin and apyrase. Pretreatment of platelets with 7E3, SZ-1 or apyrase significantly inhibited TCIPA, while pretreatment with aspirin had no effect. Moreover, combined pretreatment of platelets with 7E3, SZ-1 and apyrase significantly inhibited TCIPA, compared to single inhibitors. Combinations of antiplatelet drugs may represent a promising strategy to prevent cancer metastasis.
Keywords: adenosine diphosphate; breast cancer; glycoprotein-IIb/IIIa; glycoprotein-Ib-IX; thromboxane A2; tumor cell-induced platelet aggregation.