Inhibitory effect of recombinant fibronectin polypeptides on the adhesion of liver-metastatic lymphoma cells to hepatic sinusoidal endothelial cells and tumor invasion.
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-1 beta monoclonal antibody (mAb). Synthetic sialyl Le(x) (SLe(x)) 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 SLe(x) and SLe(a) 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 carboxymethyl-chitin, which can bind to the heparin-binding domain of CH-271. In addition, CH-271 inhibited not only tumor-endothelium interaction but also tumor cell invasion into reconstituted basement membrane Matrigel in vitro.
Yoneda
J
J
Institute of Immunological Science, Hokkaido University, Sapporo.
Saiki
I
I
Kobayashi
H
H
Fujii
H
H
Ishizaki
Y
Y
Kato
I
I
Kiso
M
M
Hasegawa
A
A
Azuma
I
I
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001485:Basement Membrane / Q000473:pathology; D002240:Carbohydrate Sequence; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology; D017077:Culture Media, Conditioned; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D005353:Fibronectins / Q000494:pharmacology*; D007375:Interleukin-1 / Q000276:immunology / Q000502:physiology; D008099:Liver / Q000098:blood supply*; D008113:Liver Neoplasms / Q000556:secondary*; D008223:Lymphoma / Q000473:pathology*; D051379:Mice; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009844:Oligosaccharides / Q000032:analysis / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins / Q000494:pharmacology; D000080506:Sialyl Lewis X Antigen; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D019040:E-Selectin; D005353:Fibronectins; D007375:Interleukin-1; D009844:Oligosaccharides; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D000080506:Sialyl Lewis X Antigen