Eicosanoid Metabolism and Tumor Cell Endothelial Cell Adhesion

The intravascular transport of tumor cells and their attachment to the vessel wall are important steps in metastasis. However, little is known about the intracellular mechanisms which regulate tumor cell adhesion to the vessel wall, particularly, to intact endothelial cells. A number of studies have suggested that circulating tumor cells preferentially adhere to the exposed underlying extracellular matrix rather than to intact endothelial cells (1,2). However, other studies suggest that tumor cells can also adhere to endothelial cells, and that this adherence is dependant upon specific characteristics of the endothelium. It has also been suggested that the metabolic characteristics of tumor cells themselves influence their own adhesion to the vessel wall (3—4). Finally, a number of recent studies suggest that adhesion receptor molecules are expressed following cell stimulation, facilitating cell/cell adhesion (5—7). In this paper we will focus on the possible intracellular regulation of expression of these adhesion molecules by two lipoxygenase derived fatty acid metabolites synthesized from arachidonic and linoleic acids. In particular, we will review the relationship between 13-hydroxyoctadecadienoic acid (13-HODE) derived from linoleic acid and 15-hydroxyeicosatetraenoic acid (15-HETE) derived from arachidonic acid, and tumor cell endothelial cell adhesion.