Increased endothelial cell retraction and tumor cell invasion by soluble factors derived from pancreatic cancer cells

Tumor cells induce endothelial cell retraction before invasion. In pancreatic cancer cells, the factors affecting endothelial cell retraction are not well-understood. The activities of the endothelial cell retraction in conditioned media (CM) derived from three 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. The CM derived from the three pancreatic cancer cells induced endothelial cell retraction. The endothelial cell retraction 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 enhanced both the adhesion and the invasion of MiaPaca-2 and Capan-1 cells. The factors with endothelial cell retraction activity in the CM from PSN-1 cells were characterized as heat-stable, trypsin-sensitive glycoproteins ranging from 10,000 to 50,000 in molecular weight, and were found both in heparin-bound and unbound fractions. PSN-1 cells produced and secreted at least two factors inducing the endothelial cell retraction. The factors could play an important role in the establishment of invasion and metastasis of PSN-1 cells.