Recombinant human prothrombin kringles have potent anti-angiogenic activities and inhibit Lewis lung carcinoma tumor growth and metastases

Tae H. Kim, Eunkyung Kim, Dongwon Yoon, Jaebeum Kim, Tai Y. Rhim, Soung S. Kim

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Prothrombin, a protein involved in blood coagulation, is a plasma glycoprotein composed of the Gla domain, two adjacent kringle domains, and a serine protease domain. Kringles are triple-disulfide-loop folding domains, which are found in several other blood proteins. In this study, we showed that recombinant human prothrombin kringle-1, -2, and -1-2 (rk-1, -2, -1-2) all have potent anti-angiogenic activities, which inhibit Lewis lung carcinoma (LLC) tumor growth and metastases. Recombinant human prothrombin kringles were expressed by an E. coli expression system and purified to apparent homogeneity from crude E. coli extracts. Purified rk-1, -2, -1-2 migrated with a molecular mass of 14, 19, and 31 kDa, respectively, on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions. rk-1, -2, -1-2 exhibited potent inhibitory effects on bFGF-stimulated bovine capillary endothelial cell growth with half-maximal concentrations (ED50) of approximately 41, 55, and 156 nM, respectively. All of the recombinant human prothrombin kringles also inhibited angiogenesis in the chorioallantoic membrane (CAM) of chick embryos at a dose of 20 μg. Systemic administration of rk-1, -2, -1-2 at a dose of 0.5 mg/kg/day suppressed the growth of primary LLC and at dose of 0.5 and 1.0 mg/kg/day inhibited LLC metastases in C57BL6/J mice lungs through their anti-angiogenic effects.

Original languageEnglish
Pages (from-to)191-201
Number of pages11
JournalAngiogenesis
Volume5
Issue number3
DOIs
Publication statusPublished - 2002 Jan 1

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Kringles
Lewis Lung Carcinoma
Prothrombin
Tumors
Neoplasm Metastasis
Growth
Escherichia coli
Neoplasms
Endothelial cells
Cell growth
Molecular mass
Serine Proteases
Chorioallantoic Membrane
Coagulation
Electrophoresis
Sodium Dodecyl Sulfate
Disulfides
Blood Proteins
Blood Coagulation
Chick Embryo

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cancer Research

Cite this

Kim, Tae H. ; Kim, Eunkyung ; Yoon, Dongwon ; Kim, Jaebeum ; Rhim, Tai Y. ; Kim, Soung S. / Recombinant human prothrombin kringles have potent anti-angiogenic activities and inhibit Lewis lung carcinoma tumor growth and metastases. In: Angiogenesis. 2002 ; Vol. 5, No. 3. pp. 191-201.
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abstract = "Prothrombin, a protein involved in blood coagulation, is a plasma glycoprotein composed of the Gla domain, two adjacent kringle domains, and a serine protease domain. Kringles are triple-disulfide-loop folding domains, which are found in several other blood proteins. In this study, we showed that recombinant human prothrombin kringle-1, -2, and -1-2 (rk-1, -2, -1-2) all have potent anti-angiogenic activities, which inhibit Lewis lung carcinoma (LLC) tumor growth and metastases. Recombinant human prothrombin kringles were expressed by an E. coli expression system and purified to apparent homogeneity from crude E. coli extracts. Purified rk-1, -2, -1-2 migrated with a molecular mass of 14, 19, and 31 kDa, respectively, on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions. rk-1, -2, -1-2 exhibited potent inhibitory effects on bFGF-stimulated bovine capillary endothelial cell growth with half-maximal concentrations (ED50) of approximately 41, 55, and 156 nM, respectively. All of the recombinant human prothrombin kringles also inhibited angiogenesis in the chorioallantoic membrane (CAM) of chick embryos at a dose of 20 μg. Systemic administration of rk-1, -2, -1-2 at a dose of 0.5 mg/kg/day suppressed the growth of primary LLC and at dose of 0.5 and 1.0 mg/kg/day inhibited LLC metastases in C57BL6/J mice lungs through their anti-angiogenic effects.",
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Recombinant human prothrombin kringles have potent anti-angiogenic activities and inhibit Lewis lung carcinoma tumor growth and metastases. / Kim, Tae H.; Kim, Eunkyung; Yoon, Dongwon; Kim, Jaebeum; Rhim, Tai Y.; Kim, Soung S.

In: Angiogenesis, Vol. 5, No. 3, 01.01.2002, p. 191-201.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Recombinant human prothrombin kringles have potent anti-angiogenic activities and inhibit Lewis lung carcinoma tumor growth and metastases

AU - Kim, Tae H.

AU - Kim, Eunkyung

AU - Yoon, Dongwon

AU - Kim, Jaebeum

AU - Rhim, Tai Y.

AU - Kim, Soung S.

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N2 - Prothrombin, a protein involved in blood coagulation, is a plasma glycoprotein composed of the Gla domain, two adjacent kringle domains, and a serine protease domain. Kringles are triple-disulfide-loop folding domains, which are found in several other blood proteins. In this study, we showed that recombinant human prothrombin kringle-1, -2, and -1-2 (rk-1, -2, -1-2) all have potent anti-angiogenic activities, which inhibit Lewis lung carcinoma (LLC) tumor growth and metastases. Recombinant human prothrombin kringles were expressed by an E. coli expression system and purified to apparent homogeneity from crude E. coli extracts. Purified rk-1, -2, -1-2 migrated with a molecular mass of 14, 19, and 31 kDa, respectively, on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions. rk-1, -2, -1-2 exhibited potent inhibitory effects on bFGF-stimulated bovine capillary endothelial cell growth with half-maximal concentrations (ED50) of approximately 41, 55, and 156 nM, respectively. All of the recombinant human prothrombin kringles also inhibited angiogenesis in the chorioallantoic membrane (CAM) of chick embryos at a dose of 20 μg. Systemic administration of rk-1, -2, -1-2 at a dose of 0.5 mg/kg/day suppressed the growth of primary LLC and at dose of 0.5 and 1.0 mg/kg/day inhibited LLC metastases in C57BL6/J mice lungs through their anti-angiogenic effects.

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