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 recombi nant fibronectin fragments with cell- and/or heparin-binding domains ( C-274, H-271 or the fusion fragment CH-271). Pretreatment of hepatic s inusoidal endothelial (HSE) cell monolayers with lymphoma cells or the ir conditioned medium for 4 to 6 h resulted in the enhancement of lymp homa cell adhesion to HSE cell monolayer, The increased tumor adhesive ness was completely abolished by preincubation of the conditioned medi um with anti interleukin-1 beta monoclonal antibody (mAb). Synthetic s ialyl Le(x) (SLe(x)) as a ligand for endothelial cell leukocyte adhesi on molecule-1 (ELAM-1) adhesion receptor and anti ELAM-1 mAb blocked t he conditioned medium-induced enhancement of tumor-endothelial cell in teraction, while pretreatment of the activated HSE cell monolayer with anti vascular cell adhesion molecule-1 (VCAM-1) mAb did not affect th e enhanced tumor cell adhesion. These results indicate that tumor cell interaction with the stimulated HSE cells is mediated by ELAM-1 molec ules 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-me diated enhancement of tumor cell adhesion to HSE monolayer was also in hibited in a concentration-dependent manner by CH-271 fusion polypepti de or the sulfated chitin derivative sulfated carboxymethyl-chitin, wh ich can bind to the heparin binding domain of CH-271. In addition, CH- 271 inhibited not only tumor-endothelium interaction but also tumor ce ll invasion into reconstituted basement membrane Matrigel in vitro.