INCREASED ENDOTHELIAL-CELL RETRACTION AND TUMOR-CELL INVASION BY SOLUBLE FACTORS DERIVED FROM PANCREATIC-CANCER CELLS

Background: Tumor cells induce endothelial cell retraction before inva sion. In pancreatic cancer cells, the factors affecting endothelial ce ll retraction are not well-understood. Methods: The activities of the endothelial cell retraction in conditioned media (CM) derived from thr ee human pancreatic cancer cell lines, PSN-1, MiaPaca-2, and Capan-1, were measured for the amount of intercellular junctional transport of FITC dextran through an endothelial cell monolayer in a transwell cell culture system. Results: The CM derived from the three pancreatic can cer cells induced endothelial cell retraction. The endothelial cell re traction activity in the CM from PSN-1 cells was significantly higher than those from MiaPaca-2 and Capan-1 cells. The CM from PSN-1 cells e nhanced both the adhesion and the invasion of MiaPaca-2 and Capan-1 ce lls. The factors with endothelial cell retraction activity in the CM f rom PSN-1 cells were characterized as heat-stable, trypsin-sensitive g lycoproteins ranging from 10,000 to 50,000 in molecular weight, and we re found both in heparin-bound and unbound fractions. Conclusions: PSN -1 cells produced and secreted at least two actors inducing the endoth elial cell retraction. The factors could play an important role in the establishment of invasion and metastasis of PSN-1 cells.