Beschreibung:
<jats:p> e15011 </jats:p><jats:p> Background: Solid tumors are notorious for their ability to form lethal metastases, sometimes several decades following initial cancer diagnosis. Development of distant metastases is a result of the primary tumor shedding cells that travel via lymphatics and the blood to distant sites where they can form metastases. Platelets are known to specifically enhance tumor cells’ survival in the bloodstream by as yet poorly understood mechanisms. To study the interplay of platelets with circulating tumor cells, we implemented our published approach to label both circulating epithelial tumor cells and platelets. Methods: Blood samples were collected from 86 non-metastatic breast cancer patients avoiding fixation and processed at 4 time points following blood collection using the maintrac approach. Samples were additionally stained with anti-CD36 antibody to visualize platelets. Results: Typically, we observed at 0h post-blood draw platelet aggregates strictly attached to single cells that did not stain with anti-EpCAM antibody. These clogged unstained cells were, by far, outnumbered by surrounding white blood cells with no platelets attached. After keeping blood samples at room temperature for 24h a completely different picture became apparent: there were still cells detectable with platelets attached to them but the underlying cell now became accessible to the anti-EpCAM antibody leading to green fluorescence staining. CETCs were detected in 94% patients on day 1 post-blood draw. The increase in single platelets in the background could be a sign that after 24h, platelets detach from CETCs. At 72 h following initial blood drawing, platelets had almost completely disappeared from the cell surface. Numbers of EpCAM-positive cells remained stable between days 1 and 3. No CETCs were observed in 2 individuals with no cancer diagnosis, neither on day zero, nor on day 1. Conclusions: Our results suggest that platelets play a key role in masking circulating tumor cells. Masking may explain the difficulties in detection of these cells and prevention of their elimination by the immune system. Our unmasking approach detects sufficient numbers of circulating tumor cells to monitor the effect on blood tumor cells of different therapeutic measures, thus contributing to improved systemic therapies for cancer. </jats:p>