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CC-BY 4.0 · TH Open 2017; 01(02): e155-e163
DOI: 10.1055/s-0037-1613674
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Release of Prometastatic Platelet-Derived Microparticles Induced by Breast Cancer Cells: A Novel Positive Feedback Mechanism for Metastasis

Marta Zarà   *
1   Department of Biology and Biotechnology, University of Pavia, Pavia, Italy
,
Gianni Francesco Guidetti   *
1   Department of Biology and Biotechnology, University of Pavia, Pavia, Italy
,
Daniela Boselli
2   FRACTAL – San Raffaele Scientific Institute, Milan, Italy
,
Chiara Villa
2   FRACTAL – San Raffaele Scientific Institute, Milan, Italy
,
Ilaria Canobbio
1   Department of Biology and Biotechnology, University of Pavia, Pavia, Italy
,
Claudio Seppi
1   Department of Biology and Biotechnology, University of Pavia, Pavia, Italy
,
Caterina Visconte
1   Department of Biology and Biotechnology, University of Pavia, Pavia, Italy
,
Jessica Canino
1   Department of Biology and Biotechnology, University of Pavia, Pavia, Italy
,
Mauro Torti
1   Department of Biology and Biotechnology, University of Pavia, Pavia, Italy
› Author Affiliations
Further Information

Publication History

21 September 2017

08 November 2017

Publication Date:
15 December 2017 (online)

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Abstract

Circulating platelets and platelet-derived microparticles are regulators of cancer metastasis. In this study, we show that breast cancer cells induce platelet aggregation and lead to the release of platelet-derived microparticles. Although able to cause comparable aggregation, the highly aggressive MDA-MB-231 cells were more potent than the poorly aggressive MCF7 cells in inducing platelet-derived microparticles release, which was comparable to that promoted by thrombin. MDA-MB-231 cells were able to bind and internalize both MCF7- and MDA-MB-231-induced platelet-derived microparticles with comparable efficiency. By contrast, MCF7 cells did not interact with either type of platelet-derived microparticles. Upon internalization, only platelet-derived microparticles released by platelet stimulation with MDA-MB-231 cells, but not those released upon stimulation with MCF7 cells, caused activation of MDA-MB-231 cells and promoted the phosphorylation of selected signaling proteins, including p38MAPK and myosin light chain. Accordingly, MDA-MB-231-induced, but not MCF7-induced, platelet-derived microparticles dose-dependently stimulated migration and invasion of targeted MDA-MB-231 cells. These results identify a novel paracrine positive feedback mechanism initiated by aggressive breast cancer cell types to potentiate their invasive phenotype through the release of platelet-derived microparticles.

Keywords

cell migration - microparticles - cancer metastasis - platelet physiology

* These authors contributed equally to this work.


 

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