Breast Cancer Processes Are Modulated by Platelet‐Derived Microparticles

Abstract

Cancer is one of the leading causes of morbidity and mortality among women worldwide. Although mortality rates have been declining for years, metastasis accounts for the majority of deaths associated with the disease. An increasing number of studies show that platelets as well as platelet-derived microparticles (PMPs) play a significant role in cancer malignancy and disease progression. PMPs are small vesicles released into the circulatory system and the extracellular environment during platelet activation. PMP generation involves a process where bioactive material is transferred from platelets to the PMPs. Interestingly, PMPs have the capacity to interact with target recipient cells and transfer their bioactive cargo into these cells upon internalization. Accordingly, studies have shown that PMPs allow intercellular exchange and trafficking of bioactive material to modulate signaling and activation processes of recipient cells. We believe that PMPs represent an important source of breast cancer modulators leading to malignant features and disease progression. The objective of this study was to evaluate the impact of PMPs on breast cancer processes. More specifically, we investigated the modulating effects of PMPs on breast cancer metabolism and phenotypic processes involved in breast cancer metastasis. First, we characterized and validated the capacity of breast cancer models to internalize PMPs and their cargo using confocal microscopy and flow cytometry. Interestingly, we observed that the levels of PMPs internalization vary and are dependent of the type of breast cancer recipient cells. Using a series of biochemical and cell-based assays, we also demonstrated that the cargo of PMPs is biologically active which results in the modulation of breast cancer cell metabolism, viability and migration properties of recipient cells. Overall, we demonstrate that PMPs modulate cancer cell processes reminiscent of disease malignancy. These findings provide a better understanding of the role of PMPs and their influence as cancer disease modulators. The knowledge gained from these studies will thus foster the development of potentially new strategic interventions to help mitigate the morbidity and mortality associated with cancer disease.