1995 Fiscal Year Annual Research Report

ウロキナーゼ受容体の細胞増殖における役割の解析

Research Project

Project/Area Number	06670052
Research Institution	HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE
Principal Investigator	浦野哲盟浜松医科大学, 医学部, 助教授 (50193967)
Co-Investigator(Kenkyū-buntansha)	永井信夫浜松医科大学, 医学部, 助手 (90260281) 高田由美子浜松医科大学, 医学部, 助手 (90092981) 高田明和浜松医科大学, 医学部, 教授 (80092980)
Keywords	ウロキナーゼ受容体 / ウロキナーゼ / プラスミノーゲン・アクチベータ- / プラスミノーゲン・アクチベータ-・インヒビター
Research Abstract	(1)培養細胞株U937を用いて、uPARmRNAの発現を検討した。ホルボールエステル刺激により、uPARmRNAの発現量が増加し、細胞内及び細胞表面上のuPARのみならず細胞培養上清中の可溶性uPAR抗原量も増加した。uPARmRNAはmatureなuPARと共に、alternative splicingにより細胞膜への結合ドメインを欠く可溶性uPAR(uPARII)をcodeするmRNAも増加していた。 (2)担癌患者の血漿中の、可溶性uPAR量を測定した。肺癌患者において血漿中uPARは正常コントロールと比較して優位な高値を示し、腫瘍マーカーとしての意義も示唆された。 (3)肺癌組織中のuPAmRNAの発現量は正常組織よりも有意に高値を示したが、uPARmRNAの発現量は正常組織との間に有意な差を認めなかった。またPAI-1及びPAI-2mRNAは、腫瘍組織中において高値を示し、腫瘍内のこれらの蛋白量が高値を示した事と一致した。 (4)培養細胞株U937を用いて、細胞増殖に対するuPA及びuPAとインヒビターの影響を検討した。uPAを単独投与することにより細胞数は若干増加した。しかしインヒビターの影響は認められなかった。U937はホルボールエステル未処理ではuPARの発現量が少ないため、他のuPAR発現細胞による検討が必要と考えられた。今後の展望:細胞膜上のuPAR及びuPA、さらにはそのインヒビターが細胞増殖に深く関与していることは、従来の蛋白量の測定だけでなく、mRNA量の測定からも明かになった。現在in situhybridization法にて、これらの蛋白の産生細胞を同定中であり、腫瘍細胞増殖機構における役割が更に解明されるものと思う。

Research Products
(18 results)

All Other

All Publications (18 results)

[Publications] Nagayama,M.et al: "Plasminogen activators and their inhibitors in non-small cell lung cancer.Low content of type 2 plasminogen activator inhibitor associated with tumor dissemination." Cancer. 73(5). 1398-1405 (1994)
[Publications] Takada,Y.et al: "Effect of heparan sulfate analogue or other sulfated polysaccharides on the activation of plasminogen by t-PA or u-PA." Thromb. Res.73(5). 301-311 (1994)
[Publications] Urano T.et al: "Electric-foot-shock induced the supression of fibrinolytic activity in rats." Thromb. Res.74(6). 595-603 (1994)
[Publications] Kojima,Y.et al.: "The Significant Enhancement of Fibrinolysis by Calcium Ion in a Cell Free System. :The Shortening of Euglobulin Clot Lysis Time by Calcium Ion." Thromb. Haemostas.72(1). 113-118 (1994)
[Publications] Urano,T.,et al.: "Heparin and heparan sulphate enhancement of the inhibitory activity of plasminogen activator inhibitor type 1 toward urokinase type plasminogen activator." Biochim, Byophys. Acta. 1201. 217-222 (1994)
[Publications] Serizawa,K.,et al.: "Medroxyprogesterone acetate(mpa)increases PAI-1 secretion from huvec and elevates the plasma levels of PAI-1 in vivo." Oncology Report. 1. 1127-1130 (1994)
[Publications] Wu,K.,et al: "The Cleavage and Inactivation of Plasminogen Activator Inhibitor Type 1 by Neutrophil Elastase: The Evaluation of Its Physiological Relevance in Fibrinolysis." Blood. 86. 1056-1061 (1995)
[Publications] Urano,T.,et al: "A. Close relationships between serotonergic and fibrinolytic systems revealed by a mono-amine-oxidase inhibitor treatment in rats." Haemostasis. 25(6). 277-282 (1995)
[Publications] Urano,T.,et al: "Absence of synergism in the activity of tissue plasminogen activator and urinary plasminogen activator measured by clot lysis time." Turk J Haematol.14. 3-7 (1995)
[Publications] Urano,T.,et al: "Reexamination of the extent of the activation of lys 78-plasminogen by tissue plasminogen activator in the presence of polymerized fibrin." Haemostasis.
[Publications] 浦野哲盟等: "ストレス負荷による血小板機能及び線溶活性の変化と、血中セロトニン関連物質との関係" 生理学研究所年報. 16. 334- (1995)
[Publications] 浦野哲盟等: "plasminogen activator inhibitor type 1(PAI-1)による線溶活性制御機構" 血液と循環. 9(2). 7-14 (1995)
[Publications] Malyszko,J.,et al: "Correlation between platelet aggregation, fibrinolysis, peripheral and central serotonergic measures in subhuman primates." A therosclerosi. 110. 63-68 (1994)
[Publications] Malyszko,J.,et al: "Relationships between scrum lipids, serofonin, platelet aggregation and some fibrinolytic parameters in humans." Life Sciences. 55(21). 1619-1623 (1994)
[Publications] Takada,A.,et al: "The physiological aspects of fibrinolysis. (Review)" Thromb. Res.76(1). 1-31 (1994)
[Publications] 浦野哲盟等: "網膜静脈血栓症に対する新しい線溶療法:糖尿病と血栓" 眼科紀要. 45. 1125-1130 (1994)
[Publications] 浦野哲盟等: "t-PAの分子構造と血栓溶解機構" 病態生理. 13(9). 673-679 (1994)
[Publications] Kotani,I.,et al: "Increased procoagulant and antifibrinolytic activities in the lungs with idiopathic pulmonary fibrosis." Thromb. Res.77(6). 493-504 (1995)

1995 Fiscal Year Annual Research Report

ウロキナーゼ受容体の細胞増殖における役割の解析

Principal Investigator

浦野 哲盟 浜松医科大学, 医学部, 助教授 (50193967)

Research Products

[Publications] Nagayama,M.et al: "Plasminogen activators and their inhibitors in non-small cell lung cancer.Low content of type 2 plasminogen activator inhibitor associated with tumor dissemination." Cancer. 73(5). 1398-1405 (1994)

[Publications] Takada,Y.et al: "Effect of heparan sulfate analogue or other sulfated polysaccharides on the activation of plasminogen by t-PA or u-PA." Thromb. Res.73(5). 301-311 (1994)

[Publications] Urano T.et al: "Electric-foot-shock induced the supression of fibrinolytic activity in rats." Thromb. Res.74(6). 595-603 (1994)

[Publications] Kojima,Y.et al.: "The Significant Enhancement of Fibrinolysis by Calcium Ion in a Cell Free System. :The Shortening of Euglobulin Clot Lysis Time by Calcium Ion." Thromb. Haemostas.72(1). 113-118 (1994)

[Publications] Urano,T.,et al.: "Heparin and heparan sulphate enhancement of the inhibitory activity of plasminogen activator inhibitor type 1 toward urokinase type plasminogen activator." Biochim, Byophys. Acta. 1201. 217-222 (1994)

[Publications] Serizawa,K.,et al.: "Medroxyprogesterone acetate(mpa)increases PAI-1 secretion from huvec and elevates the plasma levels of PAI-1 in vivo." Oncology Report. 1. 1127-1130 (1994)

[Publications] Wu,K.,et al: "The Cleavage and Inactivation of Plasminogen Activator Inhibitor Type 1 by Neutrophil Elastase: The Evaluation of Its Physiological Relevance in Fibrinolysis." Blood. 86. 1056-1061 (1995)

[Publications] Urano,T.,et al: "A. Close relationships between serotonergic and fibrinolytic systems revealed by a mono-amine-oxidase inhibitor treatment in rats." Haemostasis. 25(6). 277-282 (1995)

[Publications] Urano,T.,et al: "Absence of synergism in the activity of tissue plasminogen activator and urinary plasminogen activator measured by clot lysis time." Turk J Haematol.14. 3-7 (1995)

[Publications] Urano,T.,et al: "Reexamination of the extent of the activation of lys 78-plasminogen by tissue plasminogen activator in the presence of polymerized fibrin." Haemostasis.

[Publications] 浦野哲盟等: "ストレス負荷による血小板機能及び線溶活性の変化と、血中セロトニン関連物質との関係" 生理学研究所年報. 16. 334- (1995)

[Publications] 浦野哲盟等: "plasminogen activator inhibitor type 1(PAI-1)による線溶活性制御機構" 血液と循環. 9(2). 7-14 (1995)

[Publications] Malyszko,J.,et al: "Correlation between platelet aggregation, fibrinolysis, peripheral and central serotonergic measures in subhuman primates." A therosclerosi. 110. 63-68 (1994)

[Publications] Malyszko,J.,et al: "Relationships between scrum lipids, serofonin, platelet aggregation and some fibrinolytic parameters in humans." Life Sciences. 55(21). 1619-1623 (1994)

[Publications] Takada,A.,et al: "The physiological aspects of fibrinolysis. (Review)" Thromb. Res.76(1). 1-31 (1994)

[Publications] 浦野哲盟等: "網膜静脈血栓症に対する新しい線溶療法:糖尿病と血栓" 眼科紀要. 45. 1125-1130 (1994)

[Publications] 浦野哲盟等: "t-PAの分子構造と血栓溶解機構" 病態生理. 13(9). 673-679 (1994)

[Publications] Kotani,I.,et al: "Increased procoagulant and antifibrinolytic activities in the lungs with idiopathic pulmonary fibrosis." Thromb. Res.77(6). 493-504 (1995)

浦野哲盟浜松医科大学, 医学部, 助教授 (50193967)