Plasmin-induced migration of endothelial cells

A potential target for the anti-angiogenic action of angiostatin

Takehiko Tarui, Mousumi Majumdar, Lindsey A. Miles, Wolfram Ruf, Yoshikazu Takada

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Angiostatin, a plasminogen fragment containing 3-4 N-terminal kringle domains, is a potent inhibitor of tumor-induced angiogenesis, but its mechanism of action is unclear. Angiostatin is a ligand for integrin αvβ3 but does not induce stress fiber formation upon integrin binding, suggesting that angiostatin is a potential integrin antagonist. Plasmin, the parent molecule of angiostatin and a major extracellular protease, induces platelet aggregation, migration of peripheral blood monocytes, and release of arachidonate and leukotriene from several cell types. In the current study, we found that plasmin specifically bound to αvβ3 through the kringle domains and induced migration of endothelial cells. In contrast, angiostatin did not induce cell migration. Notably, angiostatin, anti-αvβ3 antibodies, RGD- peptide, and a serine protease inhibitor effectively blocked plasmin-induced cell migration. These results suggest that plasmin-induced migration of endothelial cells requires αvβ3 and the catalytic activity of plasmin and that this process is a potential target for the inhibitory activity of angiostatin.

Original languageEnglish
Pages (from-to)33564-33570
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number37
DOIs
Publication statusPublished - Sep 13 2002
Externally publishedYes

Fingerprint

Angiostatins
Fibrinolysin
Endothelial cells
Endothelial Cells
Integrins
Kringles
Cell Movement
Stress Fibers
Serine Proteinase Inhibitors
Leukotrienes
Plasminogen
Platelets
Platelet Aggregation
Tumors
Monocytes
Anti-Idiotypic Antibodies
Catalyst activity
Blood
Peptide Hydrolases
Agglomeration

ASJC Scopus subject areas

  • Biochemistry

Cite this

Plasmin-induced migration of endothelial cells : A potential target for the anti-angiogenic action of angiostatin. / Tarui, Takehiko; Majumdar, Mousumi; Miles, Lindsey A.; Ruf, Wolfram; Takada, Yoshikazu.

In: Journal of Biological Chemistry, Vol. 277, No. 37, 13.09.2002, p. 33564-33570.

Research output: Contribution to journalArticle

Tarui, Takehiko ; Majumdar, Mousumi ; Miles, Lindsey A. ; Ruf, Wolfram ; Takada, Yoshikazu. / Plasmin-induced migration of endothelial cells : A potential target for the anti-angiogenic action of angiostatin. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 37. pp. 33564-33570.
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