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

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 plateletderived
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.