Details

Autor(en) / Beteiligte

• Gomes, Fausto G.
• Sandim, Vanessa
• Almeida, Vitor H.
• Rondon, Araci M.R.
• Succar, Barbara B.
• Hottz, Eugenio D.
• Leal, Ana Carolina
• Verçoza, Brunno Renato F.
• Rodrigues, Juliany Cola F.
• Bozza, Patrícia T.
• Zingali, Russolina B.
• Monteiro, Robson Q.

Titel

Breast-cancer extracellular vesicles induce platelet activation and aggregation by tissue factor-independent and -dependent mechanisms

Ist Teil von

• Thrombosis research, 2017-11, Vol.159, p.24-32

Ort / Verlag

United States: Elsevier Ltd

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• Cancer-associated thrombosis is one of the major causes of worse prognosis among tumor-bearing patients. Extracellular vesicles derived from cancer cells, which can be divided mainly into microvesicles and exosomes, can participate in several tumor progression phenomena. Tumor-derived microvesicles positive for tissue factor (TF) have been associated with thrombotic risk in certain cancer types. Cancer cell-derived exosomes, however, have not. In this study we evaluated the capacity of extracellular vesicles (EVs, containing both microvesicles and exosomes) derived from breast-cancer cell lines in promoting platelet activation, aggregation and plasma coagulation, in experiments that access both TF-dependent and -independent activities. EVs were isolated from the conditioned media of two human mammary carcinoma cell lines: MDA-MB-231 (highly invasive) and MCF-7 (less invasive). TF-independent EV/platelet interaction, platelet P-selectin exposure and aggregation were evaluated. Western blotting, plasma clotting and platelet aggregation in the presence of plasma were performed for the measurement of TF-dependent activity in EVs. Interaction between MDA-MB-231 EVs and washed platelets led to increased platelet P-selectin exposure and platelet aggregation compared to MCF-7 EVs. MDA-MB-231 EVs had higher TF protein levels and TF-dependent procoagulant activity than MCF-7 EVs. Consequently, TF-dependent platelet aggregation was also induced by MDA-MB-231 EVs, but not by MCF-7 EVs. Our results suggest that MDA-MB-231 EVs induce TF-independent platelet activation and aggregation, as well as TF-dependent plasma clotting and platelet aggregation by means of thrombin generation. In this context, aggressive breast cancer-derived EVs may contribute to cancer-associated thrombosis. •Extracellular vesicles (EVs) derived from breast cancer cell lines interact with platelets.•MDA-MB-231 EVs induce TF-independent platelet activation and aggregation.•MDA-MB-231 EVs induce TF-dependent plasma clotting.•Thrombin generated by MDA-MB-231 EVs promotes platelet aggregation in plasma.•MCF-7 EVs were very much less efficient in eliciting pro-hemostatic responses.