Abstract 4846: Mitochondria packaged from platelet-derived microvesicles modulate the metabolism and mitochondrial dynamics of breast cancer cells

Abstract

Abstract The incidence of breast cancer among women far exceeds those of other cancers where metastasis accounts for the majority of deaths associated with the disease. It is well established that platelets play a prominent role in breast cancer malignancy and disease progression. Recently, activated platelets have been characterized to release platelet-derived microparticles (PMPs), which can also package functional mitochondria of platelet origin (termed mitoMPs). We recently demonstrated that mitoMPs can interact with breast cancer cells where they transfer their cargo (i.e., mitochondria) to recipient cancer cells upon their internalization. Given that metabolic reprogramming through mitochondrial dynamics represents a hallmark trait of cancer progression, the intercellular trafficking of foreign mitochondria provided by mitoMPs represent a new mechanistic avenue for cancer cell metabolic plasticity and disease progression.Therefore, the aim of this study was to evaluate the impact of mitoMP-packaged mitochondria on recipient breast cancer cell mitochondrial dynamics upon internalization. Technically, a series of breast cancer cell models (MB231, MCF7 and MCF10A) were co-cultured with mitoMPs and profiled for mitochondrial dynamics and function using complementing experimental approaches, such as flow cytometry, confocal microscopy, and RT-qPCR. We show that mitoMPs and their mitochondria cargo internalize primarily into the malignant MB231 cell model. To investigate the impact of mitoMP uptake by cancer cells on the mitochondrial dynamics, RT-qPCR and Western blot analyses were performed to profile the expression levels of several fusion and fission proteins, including OPA1, MFF, DRP1, MitoFusin 1 and MitoFusin 2. Finally, using fluorescent-based assays, we confirmed that mitoMPs modulated ATP production in MB231 breast cancer cells through upregulation of the OXPHOS pathway. Our research provides a new mechanism by which extracellular vesicles (mitoMPs) play an important role in cancer cell mitochondrial dynamics and function to support metabolic plasticity during the metastatic journey of cancer cells. The knowledge gained from these studies will further provide new avenues for strategic intervention to mitigate the morbidity and mortality associated with breast cancer disease. Citation Format: Vanessa L. Gauvin, Vanessa Veilleux, Nicolas Pichaud, Gilles A. Robichaud, Luc H. Boudreau. Mitochondria packaged from platelet-derived microvesicles modulate the metabolism and mitochondrial dynamics of breast cancer cells. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4846.