Anti-coagulant Factors Inhibits the Metastatic Activity of Tumor Cells

1999 Fiscal Year Final Research Report Summary

• Project/Area Number: 10672055
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Teikyo University
• Principal Investigator: HORIE Shuichi Teikyo University, Faculty of Pharmaceutical Science, Department of Clinical Biochemistry, Associate Professor, 薬学部, 助教授 (60157063)
• Project Period (FY): 1998 – 1999
• Keywords: Anticoagulation Factors / Tumor Cells / Cancer / Metastasis / Thrombomodulin / Tissue Factor / Extracellular matrix / Antibody

Research Abstract

By studies on the relation between expressions of anti-coagulant factors and metastatic activities of pancreatic tumor cells, BxPC-3, MIA PaCa-1, and PANC-2, following results were obtained.
1. Tumor metastatic activity measured by use of chemotaxis chamber, which was divided by a kind of extracellular matrix coated on a filter, was highly dependent on the composition of the matrix, and BxPC-3 and MIA PaCa-1 cells prefer gelatin and vitronectin, respectively, for their inversion.
2. BxPC-3 cells expressed continuously both thrombomodulin ? and tissue factor (TF), and the decrease and the increase in TM and TF, respectively, caused by treatment with various agents, such as TNF-α, IL-1β and PMA, correlated to the invasive activity.
3. Treatment of BxPC-3 cells with anti-TM IgG and anti-TF IgG increased and decreased, respectively, the activity of the cells, whereas none of change was observed in MIA PaCa-1 cells treated with anti-TF pathway inhibitor IgG. Using monoclonal antibodies of TM, the inhibitory activity of TM against tumor inversion was thought to be associated with the domain that could be interacted with protein C. However, both activated protein C and degradation products of factor Va did not inhibit the tumor inversion.
4. Transfection of expression plasmid of TM into MIA PaCa-1 cells, those were not expressed TM, resulted in does-dependent decrease in the invasive activity of the cells.
5. Factor X and Xa did not enhance the metastatic activity of tumor cells, while factor VIIa increased the activity. The TF-dependent increase in the metastasis was blocked by the pretreatment with anti-VII IgG, indicating that the complex of TF-VIIa involved directly in intracellular signaling for the expression of matrix metalloproteases.