Impact of platelet-derived mitochondria transfer in the metabolic profiling and progression of metastatic MDA-MB-231 human triple-negative breast cancer cells

Lucas Cereceda, J. Cesar Cardenas, Maroun Khoury, Eduardo Silva-Pavez*, Yessia Hidalgo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: An active role of platelets in the progression of triple-negative breast cancer (TNBC) cells has been described. Even the role of platelet-derived extracellular vesicles on the migration of MDA-MB-231 cells has been reported. Interestingly, upon activation, platelets release functional mitochondria into the extracellular environment. However, the impact of these platelet-derived mitochondria on the metabolic properties of MDA-MB-231 cells remains unclear. Methods: MDA-MB-231 and MDA-MB-231-Rho-0 cells were co-cultured with platelets, which were isolated from donor blood. Mitochondrial transfer was assessed through confocal microscopy and flow cytometry, while metabolic analyses were conducted using a Seahorse XF HS Mini Analyzer. The mito-chondrial DNA (mtDNA) copy number was determined via quantitative PCR (qPCR) following platelet co-culture. Finally, cell proliferation and colony formation assay were performed using crystal violet staining. Results and Discussion: We have shown that platelet-derived mitochondria are internalized by MDA-MB-231 cells in co-culture with platelets, increasing ATP production, oxygen (O2) consumption rate (OCR), cell proliferation, and metabolic adaptability. Additionally, we observed that MDA-MB-231 cells depleted from mtDNA restore cell proliferation in uridine/pyruvate-free cell culture medium and mitochondrial O2 consumption after co-culture with platelets, indicating a reconstitution of mtDNA facilitated by platelet-derived mitochondria. In conclusion, our study provides new insights into the role of platelet-derived mitochondria in the metabolic adaptability and progression of metastatic MDA-MB-231 TNBC cells.

Original languageEnglish
Article number1324158
JournalFrontiers in Cell and Developmental Biology
Volume11
DOIs
StatePublished - 2023

Bibliographical note

Publisher Copyright:
Copyright © 2024 Cereceda, Cardenas, Khoury, Silva-Pavez and Hidalgo.

Keywords

  • cancer
  • metabolic adaptability
  • mitochondria transfer
  • platelet-derived mitochondria
  • platelets

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