Inhibitory Effect of Recombinant Fibronectin Polypeptides on the Adhesion of Liver‐metastatic Lymphoma Cells to Hepatic Sinusoidal Endothelial Cells and Tumor Invasion

Junya Yoneda, Ikuo Saiki, Hideo Kobayashi, Hideki Fujii, Yukuo Ishizaki, Ikunoshin Kato, Makoto Kiso, Akira Hasegawa, Ichiro Azuma

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18 Citations (Scopus)

Abstract

We have investigated the inhibitory mechanism of the initial arrest of L5178Y‐ML25 lymphoma cells in a target organ (liver) by using recombinant fibronectin fragments with cell‐ and/or heparin‐binding domains (C‐274, H‐271 or the fusion fragment CH‐271). Pretreatment of hepatic sinusoidal endothelial (HSE) cell monolayers with lymphoma cells or their conditioned medium for 4 to 6 h resulted in the enhancement of lymphoma cell adhesion to HSE cell monolayer. The increased tumor adhesiveness was completely abolished by preincubation of the conditioned medium with anti interleukin‐1β monoclonal antibody (mAb). Synthetic sialyl Lex (SLex) as a ligand for endothelial cell leukocyte adhesion molecule‐1 (ELAM‐1) adhesion receptor and anti ELAM‐1 mAb blocked the conditioned medium‐induced enhancement of tumor‐endothelial cell interaction, while pretreatment of the activated HSE cell monolayer with anti vascular cell adhesion molecule‐1 (VCAM‐1) mAb did not affect the enhanced tumor cell adhesion. These results indicate that tumor cell interaction with the stimulated HSE cells is mediated by ELAM‐1 molecules on HSE cells. However, the expression of SLex and SLea on the tumor surface was not observed by flow cytometric analysis. ELAM‐1‐mediated enhancement of tumor cell adhesion to HSE monolayer was also inhibited in a concentration‐dependent manner by CH‐271 fusion polypeptide or the sulfated chitin derivative sulfated carboxyntethyl‐chitin, which can bind to the heparin‐binding domain of CH‐271. In addition, CH‐271 inhibited not only tumor‐endothelium interaction hut also tumor cell invasion into reconstituted basement membrane Matrigel in vitro.

Original languageEnglish
Pages (from-to)723-734
Number of pages12
JournalJapanese Journal of Cancer Research
Volume85
Issue number7
DOIs
Publication statusPublished - 1994 Jul
Externally publishedYes

Keywords

  • Cell adhesion
  • Endothelial cell
  • Liver metastasis
  • Lymphoma
  • Recombinant fibronectin fragment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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