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1996 Fiscal Year Final Research Report Summary

MOLECULAR BIOLOGIC ANALYSIS AND NEW THERAPEUTIC APPROACH IN INVASION AND METASTASIS OF PANCREATIC CANCER.

Research Project

Project/Area Number 06671299
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionOSAKA CITY UNIVERSITY

Principal Investigator

CHUNG Yong-suk  OSAKA CITY UNIVERSITY,MEDICAL SCHOOL,FIRST DEPARTMENT OF SURGERY,LECTURER, 医学部, 講師 (40188652)

Project Period (FY) 1994 – 1996
KeywordsPancreatic cancer / Carbohydrate antigen / Invasion and metastasis / ELAM-1 / Glycosylation inhibitor / Migrating ability / Motility factor / u-PA
Research Abstract

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 … More 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

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Y.Sakurai: "Identification and characterization of mobility stimalalog factor secreled from pannehbc cancer." Clinical Experimental Metastasis. 15. (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Kowazoe: "Role of urokinase-type plasminogen activator and inhibitory effect in iruason and metaslais of panceafc cancer" International Jourral of Oncology.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] SAWADA T.: "E-selection binding by pancreatic tumor cells is inhibited by cancer sera" International Journal of Cancer. 57. 901-907 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] SAWADA T.: "Role of carbohydrate antigens in cell-cell and cell to extracellular matrix adhesion on pancreatic cancer" Journal of Japanese Society of Gastroenterology. 92 (6). 968-975 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] SAWADA T.: "The role of carbohydrate antigens expression and ELAM-1 binding in liver metastasis of pancreatic cancer and possible therapeutic application of glycosylation inhibitor" Journal of Japanese Research Society of Gastroenterological Carcinogenesis. 7. 49-51 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] CHUNG Y.S.: "Contribution of carbohydrate antigens to endothelial E-selectin binding in cancer cells" Nihon Rinshou. 53. 1747-1752 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] SAKURAI Y.: "Identification and characterization of motility stimulating factor secreted from pancreatic cancer cells : Role in tumor invasion and metastasis" Clinical Experimantal Metastasis. 15 (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] KAWAZOE Y.: "Role of urokinase-type plasminogen activator and inhibitory effect in invasion and metastasis of pancreatic cancer" International Journal of Oncology. (accepted).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-09  

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