Inhibition of colon carcinoma cell lung colony formation by a soluble form of E-selectin

Gianna Mannori, Denise Santoro, Laura Carter, Christopher Corless, Richard M. Nelson, Michael P. Bevilacqua

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80 Scopus citations

Abstract

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 best 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.

Original languageEnglish (US)
Pages (from-to)233-243
Number of pages11
JournalAmerican Journal of Pathology
Volume151
Issue number1
StatePublished - Jul 18 1997

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Mannori, G., Santoro, D., Carter, L., Corless, C., Nelson, R. M., & Bevilacqua, M. P. (1997). Inhibition of colon carcinoma cell lung colony formation by a soluble form of E-selectin. American Journal of Pathology, 151(1), 233-243.