INHIBITION OF COLON-CARCINOMA CELL LUNG COLONY FORMATION BY A SOLUBLEFORM OF E-SELECTIN

During metastasis, tumor cells adhere to vascular endothelia, E-select in is an adhesive protein expressed by cytokine-activated endothelium that can support adhesion of colon cancer cells through the recognitio n of specific carbohydrate ligands. Using a series of colon carcinoma cell lines that displayed E-selectin adhesiveness and an increased met astatic capacity in cytokine-treated mice, we examined possible inhibi tion of cytokine-dependent experimental lung metastasis by a soluble f orm of E-selectin, the recombinant fusion protein E-selectin-immunoglo bulin. We found that E-selectin-immunoglobulin bound to the surfaces o f HT-29 colon carcinoma cells and blocked the formation of cytokine-in ducible experimental lung metastases; control L-selectin-immunoglobuli n also bound to HT-29 cells but had no effect on tumor cell lung colon ization, E-selectin-immunoglobulin was found to interfere with E-selec tin-dependent adhesion of HT-23 cells to activated vascular endotheliu m and to block the retention of these cells in the lung, a process tha t implies tumor cell adhesive interactions with the host vasculature, Our results demonstrate that E-selectin-immunoglobulin inhibits adhesi on and formation of lung metastases by colon carcinoma cells and sugge st that impairment of tumor cell-endothelium adhesion might represent a therapeutic approach to the metastatic diffusion of tumors.