Platelets and extracellular vesicles and their cross-talk with cancer.
Platelets play significant and varied roles in cancer progression, as detailed throughout this review series, via direct interactions with cancer cells as well as by long-range indirect interactions mediated by platelet releasates. Microvesicles (MV, also referred to as microparticles) released from activated platelets have emerged as major contributors to the platelet-cancer nexus. Interactions of platelet-derived MV (PMV) with cancer cells can promote disease progression through multiple mechanisms, but PMV also harbor anti-tumor functions. This complex relationship derives from the abilities of PMV both to bind to cancer cells as well as to non-transformed cells in the tumor microenvironment, and to transfer platelet-derived contents to the target cell, each of which can have stimulatory or modulatory effects. MV are extracellular vesicles of heterogeneous size, ranging from 100 nm to 1 µm in diameter, shed by living cells by outward budding of the plasma membrane, entrapping local cytosolic contents in an apparently stochastic manner. Hence, PMV are encapsulated by a lipid bilayer harboring surface proteins and lipids mirroring the platelet exterior, with internal components including platelet-derived mature mRNAs and pre-mRNAs, microRNAs (miRNAs) and other non-coding RNAs, proteins, second messengers, and mitochondria. Each of these elements engages in established and putative PMV functions in cancer. In addition, PMV contribute to cancer co-morbidities due to their roles in coagulation and thrombosis, and via interactions with inflammatory cells. However, separating effects of PMV from those of platelets in cancer contexts continues to be a major hurdle (Figure 1). This review will summarize our emerging understanding of the complex roles of PMV in the development and progression of cancer and cancer co-morbidities.
Authors: Sophia Lazar, Lawrence E Goldfinger