To clarify the potential involvement of
plasmin(
ogen) cascade
proteins in the cell dissociation and subsequent invasion of
pancreatic cancer cells, western blot analysis, immunocytochemistry, immunohistochemistry, and in vitro invasion assay were performed in the cell lines or tissue of
pancreatic cancer. The strong expression of
plasmin(
ogen),
urokinase type plasminogen activator (uPA) and uPA
receptor (uPAR), and apparently weak expression of the relevant
proteins were found in the
conditioned medium of dissociated (PC-1.0) and non-dissociated (PC-1)
pancreatic cancer cells, respectively. Furthermore, uPA-treatment significantly induced the expression of
plasmin(
ogen) and uPAR in the
conditioned medium of non-dissociated (PC-1)
pancreatic cancer cells. Moreover, the expression of
plasmin(
ogen) and uPAR was stronger at the invasive front than at the center of human
pancreatic cancer tissue. On the other hand,
plasmin-treatment induced the expression of
matrix metalloproteinase-2 (MMP-2), MMP-7 and MMP-9 in PC-1 cells. Simultaneously,
plasmin- or uPA-treatments obviously induced the dissociation of cell colonies and in vitro invasiveness in PC-1 cells. The
plasmin(
ogen) cascade is closely involved in the invasion of
pancreatic cancer cells and, especially in its early stage, cell dissociation. Targeting the
plasmin(
ogen) cascade may provide a new insight into molecular target
therapy based on anti-invasion and anti-
metastasis for
pancreatic cancer.