ENHANCEMENT OF IN-VITRO TUMOR-CELL TRANSCELLULAR MIGRATION BY TUMOR-CELL-SECRETED ENDOTHELIAL-CELL-RETRACTION FACTOR

To investigate the factors affecting endothelial-cell retraction, we h ave studied the interaction of tumor cells with endothelial cells in 2 human pancreatic cancer cell lines, PSN-1 and MiaPaca-2. The extent o f endothelial-cell retraction measured by the amount of intercellular junctional transport of FITC-dextran through an endothelial monolayer was increased by the addition of a conditioned medium (CM) from both c ell lines, while CM from PSN-1 cells was 2 to 3 times more potent than that from MiaPaca-2 cells. After the treatment of endothelial monolay er with CM of PSN-1 cells, the ability of both PSN-1 cells and MiaPaca cells to adhere to or invade the monolayer increased. The addition of CM from PSN-1 cells did not affect the growth rate of either the endo thelial or the tumor cells. The activity in the CM was heat-stable and bound to heparin-Sepharose, but was inactivated when treated by 0.5% trypsin. Protease inhibitors did not influence the activity. Pre-treat ment of PSN-1 cells by an inhibitor of protein synthesis, cycloheximid e, or of protein processing, benzyl-N-acetyl-alpha-D-galactosaminide, reduced endothelial-cell-retraction activity in the CM. The active sub stance in the CM fractionated in the molecular-weight range of 10,000 to 50,000. These results suggest that PSN-1 cells produce and secrete (a) soluble factor(s) that can induce endothelial-cell retraction, thu s facilitating tumor-cell invasion. (C) 1995 Wiley-Liss, Inc.