Tumor cell adhesive mechanisms and their relationship to metastasis

Despite recent advances in the diagnosis and therapy of many forms of cancer, metastasis remains the major cause of death in cancer patients. As tumors progress they become increasingly heterogeneous, giving rise to aggressive subpopulations of tumor cells that subsequently invade local tissues, the lymphatics, and the circulatory system. This invasive behavior can ultimately lead to the widespread dissemination and metastasis of the primary tumor. In hematogenous metastasis, emboli consisting of tumor cells, host cells, platelets, and fibrin are transported to distant sites where they arrest in the microvasculature prior to extravasation. It is well accepted that tumor cell adhesion plays a fundamental role in many of the stages of the metastatic process. Tumor cell interactions with extracellular matrix components of tissue, tissue boundaries (basement membranes), or cell adhesion-promoting components of plasma; influence tumor cell motility, invasiveness, and many other important aspects of the metastatic tumor cell phenotype. Tumor cell adhesion also has a rate-limiting influence at various stages within the metastatic process, such as tumor cell arrest and extravasation. In addition, the ability of the immune system to recognize and successfully eradicated tumors is also highly dependent on the adhesion of activated lymphocytes to target tumor cells. Despite the rapid accumulation of information on the molecular basis of cell adhesion, our understanding of the relationship between tumor cell adhesion and hematogenous metastasis per se is fragmented and incomplete. Nevertheless, clear progress has been made, both in understanding the molecular basis of tumor cell adhesion and its relationship to the biology of tumor metastasis. New and exciting directions have been identified that are likely to yield direct benefits in developing new therapeutic or diagnostic approaches for malignant neoplasms. Our purpose is to briefly review the molecular basis of tumor cell adhesion from the standpoint of many of the receptors involved as well as their putative ligands. The relationship between specific tumor cell adhesion events and the formation of metastatic lesions is also addressed.