How Circulating Cancer Cells Disguise: the Role of Platelets

Abstract

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. Blood samples were collected avoiding fixation from patients with non-metastatic cancer diagnoses and processed at 4 time points following blood collection. Circulating epithelial tumor cells were undetectable directly after blood collection but became visible after overnight storage at room temperature presumably due to release of platelets from the tumor cells. 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.