|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1996 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1995 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1994 : ¥800,000 (Direct Cost : ¥800,000)
1.In this study, three pancreatic cancer cell lines, SW1990, CAPAN-2 and PANC-1, were examined for their ability to bind to ELAM-1. SW1990 cells exhibited highest binding, highest surface expression of carbohydrate antigens sLe^a and sLe^x which correlated with in vivo hepatic metastatic ability. O-linked glycosylation inhibitor, benzyl-alpha-GalNAc reduced sLe^a and sLe^x expression and ELAM-1 binding of SW1990 and also inhibited liver metastasis. These findings suggested glycosylation inhibitor may have therapeutic possibility for preventing metastasis.
2.Next, the relationship between cell motility and experimental metastatic potential was examined using SW1990 and PANC-1. Serum-free conditioned medium from the highly metastatic SW1990 was found to contain a factor that stimulated the migration of the weakly metastatic PANC-1. Preincubation of PANC-1 cells with SW1990 conditioned medium (SW-C.M.) induced liver metastasis following splenic injection of PANC-1 cells in nude mice. This
factor is a heparin non-binding protein having a molecular weight of 40kDa caluculated by gel-filtration HPLC and results of characterization and preliminary purification suggest that this factor may be novel factor. These findings suggest that this motility factor may play an important role in pancreatic cancer invasion and metastasis, and complete purification will be useful in a strategy for inhibition of pancreatic cancer.
3.We also investigated the association of urokinase-type plasminogen activator (u-PA) with tumor cell invasion and hepatic metastasis using human pancreatic cancer cell lines (SW1990, PANC-1 and RWP-1). Subsequently, we examined the effect of the protease inhibitor, gabexate mesilate. SW1990 cells showed a higher u-PA activity (41.2U/ml) in substrate assay and invasiveness (21.6%IV) than PANC-1(14.3U/ml, 10.3%IV) and RWP-1 (22.1,13.5), which correlated with in vivo hapatic metastasis. Gabexate mesilate significantly reduced the u-PA activity, invasiveness, and hepatic metastasis of SW1990 cells.These findings suggested the possible application of protease inhibitors to prevent tumor invasion and metastasis. Less