Platelets, primarily known for thier crucial role in blood clotting and scab formation, also participate in other physiological processes, such as monitoring for viral or bacterial infections, mobilizing immune cells to potential infection sites, and directly combating pathogens.

A recent study by Ludwig Cancer Research has uncovered another significant function of platelets.

Researchers Bethan Psaila of Ludwig Oxford and Lauren Murphy,in a report published in Science,suggest that platelets contribute to the suppression of systemic inflammation. Moreover,their mechanism could be used to improve early and minimally invasive cancer detection and enhance the accuracy of prenatal screening.

Platelets as DNA “Sponges”

while platelets do not have their own nuclei, we discovered that thay act like sponges, mopping up the fragments of DNA that are released by dead and dying cells.

According to Psaila, “Our findings suggest platelets play an vital role in limiting the abundance of DNA fragments in plasma. Fascinatingly, we also discovered that they then release these pieces of DNA when they are activated, suggesting that platelets can deploy their DNA cargo in a manner that prevents nonspecific inflammation yet elicits targeted inflammatory responses where they’re needed, such as, say, at a site of injury.”

Cell-free (cf) DNA can contain circulating tumor cell-derived DNA (ctDNA). Advanced technologies are used to isolate and analyse ctDNA for noninvasive cancer detection and to monitor treatment responses. Though, ctDNA levels are frequently enough very low, especially in the early stages of cancer, making detection challenging and reducing the sensitivity of “liquid biopsies.”

Current diagnostic procedures isolate cfDNA from blood plasma after discarding all blood cells, including platelets. The study indicates that a significant portion of cfDNA, including tumor-derived DNA, resides within platelets, meaning this valuable source of data is currently overlooked.

murphy stated, “We’ve demonstrated that platelets take up DNA fragments that bear the mutational signatures of cancer cells. This is true not only in patients with advanced cancer but, remarkably, also in people who have pre-cancerous polyps in their colon, suggesting that platelets may offer an additional and so far untapped reservoir of cfDNA that could significantly improve the sensitivity of liquid biopsies.”

Implications for Cancer Prevention

The revelation that circulating platelets carry genetic signatures of cancer has major implications for cancer prevention strategies.

The researchers were prompted to investigate DNA in platelets due to their unique structure: a network of membrane-lined channels known as the open canalicular system. This system enables platelets to release molecules for clotting and tissue repair and to absorb substances like viral RNA and DNA.

Psaila hypothesized that platelets might also be absorbing genomic cfDNA. In collaboration with Chris Gregory at the University of Edinburgh, Psaila secured funding to validate this hypothesis, leading to significant data and further research grants.

The team, including Benjamin Schuster-Böckler from Ludwig Oxford, confirmed that platelets absorb human cfDNA in lab cultures and clinical samples.

To confirm that the DNA wasn’t from megakaryocytes, the researchers analyzed DNA from platelets of pregnant women carrying males, successfully predicting the baby’s sex by detecting Y chromosome fragments in the platelets.

Psaila noted, “Given their abundance, ease of isolation and tissue-wide perfusion, platelets are ideally positioned to serve as biosensors for genetic perturbations across tissues.”

future research will focus on clarifying the role of platelets in managing cfDNA and the consequences of DNA fragments released upon platelet activation.