Molecular pathological studies on the effect of anticoagulant protein C pathway on the regulation of tumorgenesis

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460396
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Suzuka University of Medical Science
• Principal Investigator: Suzuki Koji 鈴鹿医療科学大学, 薬学部, 教授 (70077808)
• Co-Investigator(Renkei-kenkyūsha): HAYASHI Tatsuya 三重県立看護大学, 看護学部, 教授 (00242959) ; OKAMOTO Takayuki 三重大学, 医学(系)研究科, 助教 (30378286)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: プロテインC凝固制御系 / 抗凝固因子 / 腫瘍促進作用 / プロテインCインヒビター / 抗腫瘍作用 / 活性化プロテインC / トロンボモジュリン

Outline of Final Research Achievements

Protein C inhibitor (PCI), a member of the serine protease inhibitors, physiologically inhibits an anticoagulant serine protease, activated protein C (APC) and thrombin- thrombomodulin (TM) complex. In this study, we studied the effects of host PCI on growth and metastasis of B16 melanoma (B16) cells by comparing between wild-type mice and mice transgenic for human PCI gene (hPCI-TG). B16 cells growth and metastatic nodules of B16 cells in the lungs were developed in hPCI-TG mice, and fibrin deposition in the lung in hPCI-TG mice was increased more than in wild-type mice. The invasive behavior of B16 cells observed in hPCI-TG mice was reduced by anti-human PCI IgG, APC, or soluble TM administration. Present studies suggest that PCI stimulates tumor cell growth and metastasis via its procoagulant properties, and anticoagulant proteins regulate PCI-dependent tumor cell growth and metastasis.

Free Research Field

血栓止血学