Endothelial-Tumor Cell Interactions in Vitro and in Vivo

Abstact

The development of a viable metastasis is a complex multi-step process (Poste, G. and Fidler, LL, 1980). A metastasizing cell must first detach from the primary tumor, degrade and invade the surrounding tissue before hematogenous and lymphatic dissemination can occur. Neoplastic cells are released into the circulation in large numbers, but only a few will establish a metastasis; many cells will die because they are unable to survive the hemodynamic pressure and host defense mechanisms. The arrest in the capillary bed of secondary organs is the next step, followed by extravasation into the organ parenchyma and establishment as micro-metastases. Once growth and neovascularization have occurred, metastatic lesions can produce further metastases. A major mechanism of tumor cell extravasation consists of the rapid attachment to the endothelium, followed by endothelial cell retraction, migration of tumor cells to the subendothelial matrix with the dissolution of the basement membrane (Crissman et al., 1988; Kramer and Nicolson, 1979; Lapis et al., 1988; Liotta, 1986). Disruption of the endothelial layer (Kawaguchi and Nakamura, 1986) during extravasation has also been described. The initial endothelial cell recognition precedes the extravasation of circulating tumor cells (Kawaguchi and Nakamura, 1986; Kramer and Nicolson, 1979). The location of the first capillary bed encountered only partially explains the site of metastasis formation, and tumor types that selectively disseminate to certain organs have been found in experimental and human systems (Fidler, 1990; Nicolson, 1988; Sugarbaker, 1979).