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Impact of platelet-derived mitochondria transfer in the metabolic profiling and progression of metastatic MDA-MB-231 human triple-negative breast cancer cells.
Cereceda, Lucas; Cardenas, J Cesar; Khoury, Maroun; Silva-Pavez, Eduardo; Hidalgo, Yessia.
Afiliação
  • Cereceda L; IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile.
  • Cardenas JC; Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de los Andes, Santiago, Chile.
  • Khoury M; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile.
  • Silva-Pavez E; Geroscience Center for Brain Health and Metabolism, Santiago, Chile.
  • Hidalgo Y; Buck Institute for Research on Aging, Novato, CA, United States.
Front Cell Dev Biol ; 11: 1324158, 2023.
Article em En | MEDLINE | ID: mdl-38283990
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Front Cell Dev Biol Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Chile País de publicação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Front Cell Dev Biol Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Chile País de publicação: Suíça