Abstract 3708: Platelet-derived microparticles modulate breast cancer malignant processes

Abstract

Abstract Breast cancer is one of the leading causes of morbidity and mortality among women, where metastasis accounts for the majority of deaths associated with this disease. Thus, the potential to effectively target tumor malignancy offers hope to mitigate disease progression and improve patient outcomes. It is well established that platelets promote multiple processes of metastasis cascade. Recently, platelets have received new attention for their impact in cancer through the production of platelet-derived microparticles (PMPs). Interestingly, PMPs allow intercellular exchange and trafficking of bioactive material through the internalization of these vesicles into recipient cells. As a result, the delivery of the intravesicular cargo can modulate signaling and activation processes of recipient cells. We recently identified a new subpopulation of these vesicles (termed mitoMPs) containing functional mitochondria. Given the predominant role of mitochondria in cancer malignancy, we believe that mitoMPs provide an important source of foreign mitochondria to support recipient breast cancer cells in malignancy and disease progression. We therefore set out to study the impact of mitoMPs on breast cancer metabolic and phenotypic processes involved in metastasis. Technically, PMPs were generated and purified from human blood platelets and co-incubated with various breast cell models (MB231, MCF7 and MCF10A). The physiological significance of mitoMPs in breast cancer disease was then assessed using various cellular and molecular assays. We demonstrate that the level of PMP internalization is highly dependent upon the type of breast cancer recipient cells. Furthermore, we show that the cargo of mitoMPs (notably mitochondria) is biologically active where recipient breast cancer cells acquired mitochondria-dependent functions, such as increased oxygen consumption rates and intracellular ATP production. Finally, we observe that mitoMPs promote malignant features such as cancer cell migration and invasion. Overall, we demonstrate that PMPs can modulate cancer cell activation and behaviour. These findings provide a better understanding of the extracellular tumor environment and the contribution of mitoMPs in supporting breast cancer cells through the metastatic landscape. The knowledge gained will further provide new avenues for therapeutic strategies in breast cancer patients. Citation Format: Vanessa Veilleux, Nicolas Pichaud, Luc H. Boudreau, Gilles A. Robichaud. Platelet-derived microparticles modulate breast cancer malignant processes. [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 3708.