Temporal analysis of CTC-endothelium interactions during early metastasis

Circulation represents one of the most vulnerable stages of the metastatic cascade. Synchronized expression of cell adhesion molecules (CAMs) on circulating tumor cells (CTCs) as well as endothelial cells (ECs) of target organs dynamically regulates CTC-EC adhesion and subsequent extravasation. Due to long time-scales associated with metastatic progression and low concentration of CTCs in blood, understanding of the spatiotemporal expression of CAMS remains elusive. Here, utilizing a lung specific model of breast cancer cells (MDA-MB-4175), we demonstrate that transient CTC interactions can prime ECs upregulating their ICAM-1expression in a time-dependent manner. Additionally, MDA-MB-4175 cells bind to the lung endothelium with greater efficiency as compared to HUVECs confirming the organotropic phenotype of metastatic cells. Further identification of the molecular binding partners can provide attractive therapeutic targets for metastasis inhibition.