Mitochondria Transfer by Platelet-Derived Microparticles Regulates Breast Cancer Bioenergetic States and Malignant Features

Abstract

Abstract An increasing number of studies show that platelets as well as platelet-derived microparticles (PMP) play significant roles in cancer malignancy and disease progression. Particularly, PMPs have the capacity to interact and internalize within target cells resulting in the transfer of their bioactive cargo, which can modulate the signaling and activation processes of recipient cells. We recently identified a new subpopulation of these vesicles (termed mitoMPs), which contain functional mitochondria. Given the predominant role of mitochondria in cancer cell metabolism and disease progression, we set out to investigate the impact of mitoMPs on breast cancer metabolic reprograming and phenotypic processes leading to malignancy. Interestingly, we observed that recipient cell permeability to PMP internalization varied among the breast cancer cell types evaluated in our study. Specifically, cells permissive to mitoMPs acquire mitochondrial-dependent functions, which stimulate increased cellular oxygen consumption rates and intracellular ATP levels. In addition, cancer cells co-incubated with PMPs display enhanced malignant features in terms of migration and invasion. Most importantly, the cancer aggressive processes and notable metabolic plasticity induced by PMPs were highly dependent on the functional status of the mitoMP-packaged mitochondria. These findings characterize a new mechanism by which breast cancer cells acquire foreign mitochondria resulting in the gain of metabolic processes and malignant features. A better understanding of these mechanisms may provide therapeutic opportunities through PMP blockade to deprive cancer cells from resources vital in disease progression. Implications: We show that the transfer of foreign mitochondria by microparticles modulates recipient cancer cell metabolic plasticity, leading to greater malignant processes.