1998 Fiscal Year Final Research Report Summary
Screening for diseases with molecular defects in protein C receptor
| Project/Area Number |
09671121
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Saga Medical School |
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Principal Investigator |
FUKUDOME Kenji Saga Medical School, Research Assistant Professor, 医学部, 助手 (50284625)
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| Project Period (FY) |
1997 – 1998
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| Keywords | EPCR / thrombomodulin / thrombosis / protein C / anticoagulant / endothelial cells / leukemia / direct-sequence |
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| Research Abstract |
The endothelial cell protein C receptor (EPCR) is capable of high-affinity binding specific for plasma anticoagulant protein C.Protein C circulates as a zymogen form of serine protease and functions as an anticoagulant when is converted to active form of enzyme on the endothelial cell surface. The thrombin/thrombomodulin (TM) complex has been found to mediate the catalytic reaction for the activation. We found that EPCR greatly accelerated protein C activation mediated by the complex by using transfected cell lines and function blocking anti-EPCR monoclonal antibodies. EPCR appears to be essential for protein C activation under the physiological conditions, therefore, abnormal function or expression of this molecule might cause defects in blood coagulation. We found that functional EPCR was induced in several cell lines established from glioblastoma and monoblastic leukemia patients. Peripheral blood mononuclear cells (PBMC) from patients with acute myerocytic leukemia type M4 and M5 were also positive for EPCR.In contrast, PBMC from healthy donors were negative for the antigen. EPCR could be a novel marker for some types of cancers, and abnormal expression of this molecule might explain some disorder of blood coagulation in cancer. We also developed a screening system to detect the genetic defects of EPCR.We established PCR methods to amplify the exons of EPCR and also established direct sequencing methods. Screening by using these methods is now under going.
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[Publications] Fukudome, K., Ye, X., Tsuneyoshi, N., Tokunaga, O., Sugawara, K., Mizokami, H.and Kimoto, M.: "Activation mechanism of anticoagulant protein C in large blood vessels involving the endothelial cell protein C receptor." J.Exp.Med.187. 1029-1035 (1998)
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