Platelets and tumor-associated RNA transfer

Abstract

Until recently, the nucleic acid content of platelets was considered to be fully determined by their progenitor megakaryocyte. However, it is now well understood that additional mediators (eg, cancer cells) can intervene, thereby influencing the RNA repertoire of platelets. Platelets are highly dynamic cells that are able to communicate and influence their environment. For instance, platelets have been involved in various steps of cancer development and progression by supporting tumor growth, survival, and dissemination. Cancer cells can directly and/or indirectly influence platelet RNA content, resulting in tumor-mediated "education" of platelets. Alterations in the tumor-educated platelet RNA profile have been described as a novel source of potential biomarkers. Individual platelet RNA biomarkers as well as complex RNA signatures may be used for early detection of cancer and treatment monitoring. Here, we review the RNA transfer occurring between cancer cells and platelets. We explore the potential use of platelet RNA biomarkers as a liquid biopsy biosource and discuss methods to evaluate the transcriptomic content of platelets.

Keywords: PLATELETS/Platelet interactions with other cells; Platelets; RNA; cancer; diagnostics; liquid biopsy.

© 2021 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Schematic representation of direct and indirect mechanisms of platelet RNA transfer to nucleated cells. (A) Platelets can transfer part of their content to a recipient cell through direct contact with the membrane system of the target cell, or they can be internalized by the recipient cell. (B-C) Platelets can indirectly transfer their content by releasing PMPs or P-Exos. PMPs affect cellular responses through activation of cell surface receptors, horizontal transfer of RNA in and/or on PMPs through transient interaction with cell membranes, or internalization of PMPs and release of their content directly inside the recipient cell.