Inhibition of colon carcinoma cell lung colony formation by a soluble form of E-selectin.
During metastasis, tumor cells adhere to vascular endothelia. E-selectin is an adhesive protein expressed by cytokine-activated endothelium that can support adhesion of colon cancer cells through the recognition of specific carbohydrate ligands. Using a series of colon carcinoma cell lines that displayed E-selectin adhesiveness and an increased metastatic capacity in cytokine-treated mice, we examined possible inhibition of cytokine-dependent experimental lung metastasis by a soluble form of E-selectin, the recombinant fusion protein E-selectin-immunoglobulin. We found that E-selectin-immunoglobulin bound to the surfaces of HT-29 colon carcinoma cells and blocked the formation of cytokine-inducible experimental lung metastases; control L-selectin-immunoglobulin also bound to HT-29 cells but had no effect on tumor cell lung colonization. E-selectin-immunoglobulin was found to interfere with E-selectin-dependent adhesion of HT-29 cells to activated vascular endothelium and to block the retention of these cells in the lung, a process that implies tumor cell adhesive interactions with the host vasculature. Our results demonstrate that E-selectin-immunoglobulin inhibits adhesion and formation of lung metastases by colon carcinoma cells and suggest that impairment of tumor cell-endothelium adhesion might represent a therapeutic approach to the metastatic diffusion of tumors.
Mannori
G
G
Howard Hughes Medical Institute, University of California, San Diego, La Jolla, USA.
Santoro
D
D
Carter
L
L
Corless
C
C
Nelson
R M
RM
Bevilacqua
M P
MP
D000818:Animals; D018938:Caco-2 Cells; D002240:Carbohydrate Sequence; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D016207:Cytokines / Q000502:physiology; D019040:E-Selectin / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000556:secondary*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012995:Solubility; D014407:Tumor Cells, Cultured
D016207:Cytokines; D019040:E-Selectin; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins