PLATELET BIOLOGY

In recent years, a variety of technologies that have the ability to detect disease-specific nucleic acids with the aim of diagnosing disease and therapy selection have been launched. Despite the potential of these platforms, the major hurdle is to obtain easily accessible nucleic acids for analysis, in a non-invasive way, in particular in the field of oncology. Therefore a new search for novel sources of tumor-derived nucleic acids is urgently needed to improve the accessibility and usability of current technologies.

Thrombocytes, or blood platelets, are small, irregular shaped cell fragments that circulate in our blood, and play a role in haemostasis, especially in the formation of blood cloths. Blood generally contains 200-500 million blood platelets per milliliter, which makes platelets a highly available material for research and clinical use. Moreover, blood platelet isolation is relatively simple and is a standard procedure in blood bank/haematology labs. Since platelets do not contain a nucleus, their RNA transcripts – needed for functional maintenance – are derived from megakaryocytes during platelet origination, all other RNAs are acquired during platelet ciculation. Platelet RNA can be readily isolated and subjected to genetic analysis.

We discovered that blood platelets have the ability to ingest nucleic acids, including tumor RNA, providing a safe haven for circulating disease-specific nucleic acids. We demonstrated that tumor RNA markers can be readily detected in blood platelets of cancer patients, in contrast to healthy donors, following the expression pattern in corresponding tumor tissue tissue biopsies. Bioanalyzer results and genome-wide gene expression arrays and RNA Seq revealed RNA of high quality.

It is established that tumor cells can release nucleic acids such as RNA and DNA into the circulation via a variety of mechanisms. Interest in platelets and their ability to interact with intravascular components and tumor cells have enticed several groups to pursue the use of platelets as a source for cancer biomarkers. However, any role of circulating disease-specific nucleic acids in platelet biology remains to be investigated.

Besides nucleic acid uptake by platelets, it was reported that platelets can efficiently release pro-tumoral RNA-containing microvesicles themselves, potentially accounting for more than 50% of all microvesicles present in blood. Thus, the spread of nucleic acids by tumor cells via platelets provides a strategic opening for cancer surveillance.