Platelet-derived extracellular vesicles regulate cell cycle progression and cell migration in breast cancer cells

Mauro Vismara, Marta Zarà, Sharon Negri, Jessica Canino, Ilaria Canobbio, Silvia Stella Barbieri, Francesco Moccia, Mauro Torti, Gianni Francesco Guidetti

Research output: Contribution to journalArticlepeer-review

Abstract

Platelets have been extensively implicated in the progression of cancer and platelet-derived extracellular vesicles (PEVs) are gaining growing attention as potential mediators of the platelet-cancer interplay. PEVs are shed from platelet membrane in response to extracellular stimuli and carry important biological signals for intercellular communication. In this study we demonstrate that PEVs specifically bind to different breast cancer cells and elicit cell-specific functional responses. PEVs were massively internalized by the metastatic cell lines MDA-MB-231 and SKBR3 and the ductal carcinoma cell line BT474, but not by the MCF-7 cell line. In SKBR3 cells, PEVs decreased mitochondrial dehydrogenase activities and altered cell cycle progression without affecting cell viability. Conversely, PEVs potently stimulated migration and invasion of MDA-MB-231, without affecting the distribution in the different phases of the cell cycle. In all the analyzed breast cancer cells, PEVs triggered a sustained increase of intracellular Ca2+, but only in MDA-MB-231 cells, this was associated to the stimulation of selected signaling proteins implicated in migration, including p38MAPK and myosin light chain. Importantly, inhibition of myosin light chain phosphorylation by a Rho kinase inhibitor prevented PEVs-stimulated migration of MDA-MB-231 cells. Our results demonstrate that PEVs are versatile regulators of cancer cell behavior and elicit a variety of different responses depending on the specific breast cancer cell subtype.

Original languageEnglish
Article number118886
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1868
Issue number1
DOIs
Publication statusPublished - Jan 2021

Keywords

  • Cancer
  • Extracellular vesicles
  • Platelet microparticles
  • Platelets

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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