The adhesion of cancer cells to the endothelium during the metastatic process involves the interaction of specific cell-cell adhesion receptors on the cell surface. E-selectin on endothelial cells and sialyl Lewis X carbohydrate component on tumor cells are mainly implicated in the adhesion of colon carcinoma cells to the endothelium of target organ. In this paper we show that binding of E-selectin to T84 colon tumor cells causes approximately a twofold increase in intracellular calcium concentration. In particular, using two inhibitors of receptor operated calcium channels, CAI and SK&F 96365, we present evidences that the augmentation in cytoplasmic calcium originates from ionic influx from extracellular sources. Furthermore, we demonstrated that modulation of [Ca2+](i) by engagement of E-selectin receptor starts signal transduction pathways that affect cell spreading, tyrosine phosphorylation signaling, and cancer cell motility. (C) 2003 Elsevier Science (USA). All rights reserved.