Cancer cells in transit: the vascular interactions of tumor cells

Metastasis is a highly regulated, multistep process in which cancerous cells shed from the primary tumor and enter the circulatory system, where they interact extensively with host cells before they lodge and colonize the target organ. The adhesive interactions of circulating tumor cells with platelets, leukocytes, and endothelial cells facilitate their survival and extravasation from the vasculature, thus representing critical kick-off events for the colonization of distant organs. This review presents our current mechanistic knowledge on vascular interactions of tumor cells, and it discusses biochemical and cell and molecular biology techniques used for the identification of novel receptor-ligand pairs mediating these interactions. This review brings together diverse observations about the contributions of key molecular constituents, including selectins, fibrin(ogen), and CD44, in one mechanistic interpretation. Understanding the molecular underpinnings of adhesive interactions between tumor cells and host cells may provide guidelines for developing promising antimetastatic therapies when initiated early in the course of disease progression.