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PMID: 9212748 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The American journal of pathology ·Vol. 151 ·No. 1 ·1997-07-00 ·Pages 233-43

Mannori G, Santoro D, Carter L, Corless C, Nelson RM, Bevilacqua MP

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 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.

MeSH Terms
Animals Caco-2 Cells Carbohydrate Sequence Carcinoma/drug therapy,pathology Cell Adhesion/drug effects Cell Aggregation/drug effects Colonic Neoplasms/drug therapy,pathology Cytokines/physiology E-Selectin/pharmacology Endothelium, Vascular/drug effects HT29 Cells Humans Immunoglobulin G/pharmacology Lung Neoplasms/drug therapy,pathology,secondary Male Mice Mice, Inbred BALB C Mice, Nude Molecular Sequence Data Neoplastic Stem Cells/drug effects,pathology Recombinant Fusion Proteins/pharmacology Solubility Tumor Cells, Cultured
Chemicals
Cytokines E-Selectin Immunoglobulin G Recombinant Fusion Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Mannori G
Howard Hughes Medical Institute, University of California, San Diego, La Jolla, USA.
Santoro D
Carter L
Corless C
Nelson R M
Bevilacqua M P
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
Published
1997-07-00
Pages
233-43
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1857910
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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