Platelet-Derived Extracellular Vesicles Stimulate Migration through Partial Remodelling of the Ca 2+ Handling Machinery in MDA-MB-231 Breast Cancer Cells.

Autor: Vismara, Mauro, Negri, Sharon, Scolari, Francesca, Brunetti, Valentina, Trivigno, Silvia Maria Grazia, Faris, Pawan, Galgano, Luca, Soda, Teresa, Berra-Romani, Roberto, Canobbio, Ilaria, Torti, Mauro, Guidetti, Gianni Francesco, Moccia, Francesco
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Zdroj: Cells (2073-4409); Oct2022, Vol. 11 Issue 19, p3120, 19p
Abstrakt: Background: Platelets can support cancer progression via the release of microparticles and microvesicles that enhance the migratory behaviour of recipient cancer cells. We recently showed that platelet-derived extracellular vesicles (PEVs) stimulate migration and invasiveness in highly metastatic MDA-MB-231 cells by stimulating the phosphorylation of p38 MAPK and the myosin light chain 2 (MLC2). Herein, we assessed whether the pro-migratory effect of PEVs involves the remodelling of the Ca2+ handling machinery, which drives MDA-MB-231 cell motility. Methods: PEVs were isolated from human blood platelets, and Fura-2/AM Ca2+ imaging, RT-qPCR, and immunoblotting were exploited to assess their effect on intracellular Ca2+ dynamics and Ca2+-dependent migratory processes in MDA-MB-231 cells. Results: Pretreating MDA-MB-231 cells with PEVs for 24 h caused an increase in Ca2+ release from the endoplasmic reticulum (ER) due to the up-regulation of SERCA2B and InsP3R1/InsP3R2 mRNAs and proteins. The consequent enhancement of ER Ca2+ depletion led to a significant increase in store-operated Ca2+ entry. The larger Ca2+ mobilization from the ER was required to potentiate serum-induced migration by recruiting p38 MAPK and MLC2. Conclusions: PEVs stimulate migration in the highly metastatic MDA-MB-231 breast cancer cell line by inducing a partial remodelling of the Ca2+ handling machinery. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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