Cytokines and cell adhesion molecules in tumor-endothelial cell interaction and metastasis

Metastasis is a multistep process in which a metastatic tumor cell detaches from the primary tumor, invades the surrounding tissues, passes through supporting structures such as interstitial stroma and extracellular matrix, and enters the lymphatic or blood circulation (Poste and Fidler, 1980). Only a few of the neoplastic cells released into the circulation, that survive hemodynamic pressure and host defense mechanisms, will form metastases. The arrest of tumor cells in the capillary bed of secondary organs through an interaction with vascular or lymphatic endothelium and subendothelial basement membrane is followed by their extravasation into the tissue parenchyma, and then micro-metastasis formation. Therefore cell-cell and cell-substrate adhesions occur at different moments in this process. With the recent identification and characterization of cell surface molecules, it has become of particular interest to clarify their role in tumor progression and metastasis (Albelda, 1993).