Elastase activity enhances the adhesion of neutrophil and cancer cells to vascular endothelial cells

Background. Elastase activity in cancer cells has been reported to promote their metastasis. Hence, we analyzed the influence of elastase activity of cancer cells on their responsive adhesion to vascular endothelial cells. Materials and methods. Human pancreatic (S2-007, S2-013, S2-020, S2-028) an d colonic (COLO205) cancer cell lines were used. S2-007, S2-013, and S2-020 possess high elastase activity, whereas S2-028 and COLO205 have low elasta se activity. Adhesive reactions of these cancer cells and neutrophils to TN F alpha -activated HUVEC were analyzed. Bound cells onto HUVEC were counted after incubation for 10 min. The effects of suppression of elastase activi ty by ZD8321, a potent elastase inhibitor, and supplementation of human neu trophil elastase (NE) on the adhesive reactions were also analyzed. In addi tion, E-selectin expression on HUVEC and concentrations of soluble E-select in in the medium were measured. Results. Adhesion of cells with high intracellular elastase activity to TNF alpha -activated HUVEC was suppressed by ZD8321. On the other hand, adhesi on of cells with low elastase activity was enhanced by exogenous NE. Expres sion of E-selectin, a key molecule in leukocyte-endothelial cell interactio n, on HUVEC was increased by NE. Soluble E-selectin concentration in the me dium increased after the adhesive reaction between neutrophils and HUVEC. T his increase was thought to be due to the shedding of cell surface E-select in. Such responses were inhibited by ZD8321. Conclusion. Elastase activity has a biological function of stimulating both the E-selectin expression on HUVEC and the resultant adhesive reaction of cancer cells with them. Inhibition of elastase activity is a potent strateg y for controlling cancer metastasis. (C) 2000 Academic Press.