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

Am J Pathol. 1997 Jul;151(1):233-43.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caco-2 Cells
  • Carbohydrate Sequence
  • Carcinoma / drug therapy
  • Carcinoma / pathology*
  • Cell Adhesion / drug effects
  • Cell Aggregation / drug effects
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / pathology*
  • Cytokines / physiology
  • E-Selectin / pharmacology*
  • Endothelium, Vascular / drug effects
  • HT29 Cells
  • Humans
  • Immunoglobulin G / pharmacology
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / secondary*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Sequence Data
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / pathology*
  • Recombinant Fusion Proteins / pharmacology
  • Solubility
  • Tumor Cells, Cultured

Substances

  • Cytokines
  • E-Selectin
  • Immunoglobulin G
  • Recombinant Fusion Proteins