The formation of
metastasis is a dreadful complication of
cancer that is associated with a poor prognosis. Several clinical observations and experimental findings indicate that the metastatic process is nonrandom and involves a sequence of multistep events that may all be targeted for
therapy. This includes angiogenesis of the primary
neoplasm, release of malignant cells from this
neoplasm, entry of
cancer cells into the blood circulation, interaction of
cancer cells with vascular endothelial cells in distant organs, and growth of blood-borne
cancer cells locally in the vessels or distally following extravasation. Our working hypothesis is that metastatic
cancer cells exploit the mechanisms of the
inflammation process to successfully migrate into distant organs. This implies a pivotal role for specific adhesive interactions between
cancer cells and vascular endothelial cells and activation of migratory pathways in the
cancer cells. We review here the roles played by the endothelial adhesive molecule
E-selectin and by the motogenic stress-activated
protein kinase-2 (
SAPK2/p38) pathway of
cancer cells in modulating transendothelial migration of
cancer cells.