Specific Interaction of Angiostatin with Integrin α vβ3 in Endothelial Cells

Takehiko Tarui, Lindsey A. Miles, Yoshikazu Takada

Research output: Contribution to journalArticle

184 Citations (Scopus)

Abstract

Angiostatin, the N-terminal four kringles (K1-4) of plasminogen, blocks tumor-mediated angiogenesis and has great therapeutic potential. However, angiostatin's mechanism of anti-angiogenic action is unclear. We found that bovine arterial endothelial (BAE) cells adhere to angiostatin in an integrin-dependent manner and that integrins αvβ 3, α9β1, and to a lesser extent α4β1, specifically bind to angiostatin. αvβ3 is a predominant receptor for angiostatin on BAE cells, since a function-blocking antibody to αvβ 3 effectively blocks adhesion of BAE cells to angiostatin, but an antibody to α9β1 does not. ε-Aminocaproic acid, a Lys analogue, effectively blocks angiostatin binding to BAE cells, indicating that an unoccupied Lys-binding site of the kringles may be required for integrin binding. It is known that other plasminogen fragments containing three or five kringles (K1-3 or K1-5) have an anti-angiogenic effect, but plasminogen itself does not. We found that K1-3 and K1-5 bind to α vβ3, but plasminogen does not. These results suggest that the anti-angiogenic action of angiostatin may be mediated via interaction with αvβ3. Angiostatin binding to α vβ3 does not strongly induce stress-fiber formation, suggesting that angiostatin may prevent angiogenesis by perturbing the αvβ3-mediated signal transduction that may be necessary for angiogenesis.

Original languageEnglish
Pages (from-to)39562-39568
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number43
DOIs
Publication statusPublished - Oct 26 2001
Externally publishedYes

Fingerprint

Angiostatins
Endothelial cells
Integrins
Endothelial Cells
Plasminogen
Kringles
Aminocaproic Acid
Signal transduction
Stress Fibers
Blocking Antibodies
Tumors
Signal Transduction
Adhesion

ASJC Scopus subject areas

  • Biochemistry

Cite this

Specific Interaction of Angiostatin with Integrin α vβ3 in Endothelial Cells. / Tarui, Takehiko; Miles, Lindsey A.; Takada, Yoshikazu.

In: Journal of Biological Chemistry, Vol. 276, No. 43, 26.10.2001, p. 39562-39568.

Research output: Contribution to journalArticle

Tarui, Takehiko ; Miles, Lindsey A. ; Takada, Yoshikazu. / Specific Interaction of Angiostatin with Integrin α vβ3 in Endothelial Cells. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 43. pp. 39562-39568.
@article{c62226eaec3c4d00b64ea51e6ca55012,
title = "Specific Interaction of Angiostatin with Integrin α vβ3 in Endothelial Cells",
abstract = "Angiostatin, the N-terminal four kringles (K1-4) of plasminogen, blocks tumor-mediated angiogenesis and has great therapeutic potential. However, angiostatin's mechanism of anti-angiogenic action is unclear. We found that bovine arterial endothelial (BAE) cells adhere to angiostatin in an integrin-dependent manner and that integrins αvβ 3, α9β1, and to a lesser extent α4β1, specifically bind to angiostatin. αvβ3 is a predominant receptor for angiostatin on BAE cells, since a function-blocking antibody to αvβ 3 effectively blocks adhesion of BAE cells to angiostatin, but an antibody to α9β1 does not. ε-Aminocaproic acid, a Lys analogue, effectively blocks angiostatin binding to BAE cells, indicating that an unoccupied Lys-binding site of the kringles may be required for integrin binding. It is known that other plasminogen fragments containing three or five kringles (K1-3 or K1-5) have an anti-angiogenic effect, but plasminogen itself does not. We found that K1-3 and K1-5 bind to α vβ3, but plasminogen does not. These results suggest that the anti-angiogenic action of angiostatin may be mediated via interaction with αvβ3. Angiostatin binding to α vβ3 does not strongly induce stress-fiber formation, suggesting that angiostatin may prevent angiogenesis by perturbing the αvβ3-mediated signal transduction that may be necessary for angiogenesis.",
author = "Takehiko Tarui and Miles, {Lindsey A.} and Yoshikazu Takada",
year = "2001",
month = "10",
day = "26",
doi = "10.1074/jbc.M101815200",
language = "English",
volume = "276",
pages = "39562--39568",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "43",

}

TY - JOUR

T1 - Specific Interaction of Angiostatin with Integrin α vβ3 in Endothelial Cells

AU - Tarui, Takehiko

AU - Miles, Lindsey A.

AU - Takada, Yoshikazu

PY - 2001/10/26

Y1 - 2001/10/26

N2 - Angiostatin, the N-terminal four kringles (K1-4) of plasminogen, blocks tumor-mediated angiogenesis and has great therapeutic potential. However, angiostatin's mechanism of anti-angiogenic action is unclear. We found that bovine arterial endothelial (BAE) cells adhere to angiostatin in an integrin-dependent manner and that integrins αvβ 3, α9β1, and to a lesser extent α4β1, specifically bind to angiostatin. αvβ3 is a predominant receptor for angiostatin on BAE cells, since a function-blocking antibody to αvβ 3 effectively blocks adhesion of BAE cells to angiostatin, but an antibody to α9β1 does not. ε-Aminocaproic acid, a Lys analogue, effectively blocks angiostatin binding to BAE cells, indicating that an unoccupied Lys-binding site of the kringles may be required for integrin binding. It is known that other plasminogen fragments containing three or five kringles (K1-3 or K1-5) have an anti-angiogenic effect, but plasminogen itself does not. We found that K1-3 and K1-5 bind to α vβ3, but plasminogen does not. These results suggest that the anti-angiogenic action of angiostatin may be mediated via interaction with αvβ3. Angiostatin binding to α vβ3 does not strongly induce stress-fiber formation, suggesting that angiostatin may prevent angiogenesis by perturbing the αvβ3-mediated signal transduction that may be necessary for angiogenesis.

AB - Angiostatin, the N-terminal four kringles (K1-4) of plasminogen, blocks tumor-mediated angiogenesis and has great therapeutic potential. However, angiostatin's mechanism of anti-angiogenic action is unclear. We found that bovine arterial endothelial (BAE) cells adhere to angiostatin in an integrin-dependent manner and that integrins αvβ 3, α9β1, and to a lesser extent α4β1, specifically bind to angiostatin. αvβ3 is a predominant receptor for angiostatin on BAE cells, since a function-blocking antibody to αvβ 3 effectively blocks adhesion of BAE cells to angiostatin, but an antibody to α9β1 does not. ε-Aminocaproic acid, a Lys analogue, effectively blocks angiostatin binding to BAE cells, indicating that an unoccupied Lys-binding site of the kringles may be required for integrin binding. It is known that other plasminogen fragments containing three or five kringles (K1-3 or K1-5) have an anti-angiogenic effect, but plasminogen itself does not. We found that K1-3 and K1-5 bind to α vβ3, but plasminogen does not. These results suggest that the anti-angiogenic action of angiostatin may be mediated via interaction with αvβ3. Angiostatin binding to α vβ3 does not strongly induce stress-fiber formation, suggesting that angiostatin may prevent angiogenesis by perturbing the αvβ3-mediated signal transduction that may be necessary for angiogenesis.

UR - http://www.scopus.com/inward/record.url?scp=0035955645&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035955645&partnerID=8YFLogxK

U2 - 10.1074/jbc.M101815200

DO - 10.1074/jbc.M101815200

M3 - Article

C2 - 11514539

AN - SCOPUS:0035955645

VL - 276

SP - 39562

EP - 39568

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 43

ER -