Adhesive proteins and the hematogenous spread of cancer.

The metastatic spread of cancer is a complex and multistep process characterized by a number of biological steps which include the hematogenous and lymphatic arrest and adhesion of circulating tumor cells in the vascular bed, invasion of tumor cells through the basement membrane, and growth of new tumor colonies in the organ parenchyma. In this brief review we describe the role of platelets, the hemostatic system, adhesive proteins and their putative receptors in the hematogenous dissemination of cancer. The major adhesive proteins postulated to play a role in tumor arrest in the vascular bed are thrombospondin-1 (TSP-1), laminin, fibronectin and hyaluronan-proteoglycans. The major tumor and vascular receptors mediating these adhesive interactions are the CSVTCG-specific TSP-1 receptor, the 67-kD laminin receptor, the alpha v beta 3 vitronectin/TSP-1/fibronectin receptor, and CD44 hyaluronan receptor. The discovery of the involvement of these adhesive proteins and receptors in the metastatic spread of cancer as well as components of the hemostatic system offers unique opportunities for the development of antimetastasis therapies for the treatment of cancer.