Angiostatin, a circulating inhibitor of angiogenesis, was identified by its ability to maintain dormancy of established metastases in vivo. In vitro, angiostatin inhibits endothelial cell migration, proliferation, and tube formation, and induces apoptosis in a cell type–specific manner. We have used a construct encoding the kringle domains 1–4 of angiostatin to screen a placenta yeast two-hybrid cDNA library for angiostatin-binding peptides. Here we report the identification of angiomotin, a novel protein that mediates angiostatin inhibition of migration and tube formation of endothelial cells. In vivo, angiomotin is expressed in the endothelial cells of capillaries as well as larger vessels of the human placenta. Upon expression of angiomotin in HeLa cells, angiomotin bound and internalized fluorescein-labeled angiostatin. Transfected angiomotin as well as endogenous angiomotin protein were localized to the leading edge of migrating endothelial cells. Expression of angiomotin in endothelial cells resulted in increased cell migration, suggesting a stimulatory role of angiomotin in cell motility. However, treatment with angiostatin inhibited migration and tube formation in angiomotin-expressing cells but not in control cells. These findings indicate that angiostatin inhibits cell migration by interfering with angiomotin activity in endothelial cells.
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19 March 2001
Article|
March 19 2001
Angiomotin: An Angiostatin Binding Protein That Regulates Endothelial Cell Migration and Tube Formation
Boris Troyanovsky,
Boris Troyanovsky
aCenter for Genomics Research and Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 76 Stockholm, Sweden
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Tetyana Levchenko,
Tetyana Levchenko
aCenter for Genomics Research and Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 76 Stockholm, Sweden
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Göran Månsson,
Göran Månsson
aCenter for Genomics Research and Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 76 Stockholm, Sweden
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Olga Matvijenko,
Olga Matvijenko
aCenter for Genomics Research and Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 76 Stockholm, Sweden
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Lars Holmgren
Lars Holmgren
aCenter for Genomics Research and Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 76 Stockholm, Sweden
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Boris Troyanovsky
aCenter for Genomics Research and Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 76 Stockholm, Sweden
Tetyana Levchenko
aCenter for Genomics Research and Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 76 Stockholm, Sweden
Göran Månsson
aCenter for Genomics Research and Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 76 Stockholm, Sweden
Olga Matvijenko
aCenter for Genomics Research and Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 76 Stockholm, Sweden
Lars Holmgren
aCenter for Genomics Research and Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 76 Stockholm, Sweden
B. Troyanovsky and T. Levchenko contributed equally to this work.
Abbreviations used in this paper: β-gal, β-galactosidase; bFGF, basic fibroblast growth factor; FAK, focal adhesion kinase; GFP, green fluorescent protein; GST; glutathione S-transferase; HUVEC, human umbilical vein endothelial cell; MAE, mouse aortic endothelial; RT, reverse transcription.
Received:
October 27 2000
Revision Requested:
January 12 2001
Accepted:
January 18 2001
Online ISSN: 1540-8140
Print ISSN: 0021-9525
© 2001 The Rockefeller University Press
2001
The Rockefeller University Press
J Cell Biol (2001) 152 (6): 1247–1254.
Article history
Received:
October 27 2000
Revision Requested:
January 12 2001
Accepted:
January 18 2001
Citation
Boris Troyanovsky, Tetyana Levchenko, Göran Månsson, Olga Matvijenko, Lars Holmgren; Angiomotin: An Angiostatin Binding Protein That Regulates Endothelial Cell Migration and Tube Formation. J Cell Biol 19 March 2001; 152 (6): 1247–1254. doi: https://doi.org/10.1083/jcb.152.6.1247
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