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Angiomotin: an angiostatin binding protein that regulates endothelial cell migration and tube formation.

Troyanovsky B, Levchenko T, Månsson G, Matvijenko O, Holmgren L - J. Cell Biol. (2001)

Bottom Line: 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.These findings indicate that angiostatin inhibits cell migration by interfering with angiomotin activity in endothelial cells.

View Article: PubMed Central - PubMed

Affiliation: Center for Genomics Research and Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 76 Stockholm, Sweden.

ABSTRACT
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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(A) Angiostatin inhibits tube formation of angiomotin-transfected cells plated on matrigel. MAE-vector and MAE-angiomotin transfected cells were pretreated with 5 μg/ml angiostatin for 16 h before trypsinization and plating on matrigel. Images show tube formation 16 h after seeding on matrigel (Bar, 130 μm). (B) Total tube length formed in the presence or absence of angiostatin. The data represent the average from three independent experiments (error bars = SD).
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Figure 8: (A) Angiostatin inhibits tube formation of angiomotin-transfected cells plated on matrigel. MAE-vector and MAE-angiomotin transfected cells were pretreated with 5 μg/ml angiostatin for 16 h before trypsinization and plating on matrigel. Images show tube formation 16 h after seeding on matrigel (Bar, 130 μm). (B) Total tube length formed in the presence or absence of angiostatin. The data represent the average from three independent experiments (error bars = SD).

Mentions: To further explore the role of angiomotin in mediating angiostatin inhibition of angiogenesis, we studied the effect of angiostatin on the formation of vascular structures in the matrigel tube formation assay. No detectable difference between angiomotin- and vector-transfected MAE cells in the capacity to form tubes in vitro could be detected (Fig. 8 A). However, pretreating the cells for 16 h with angiostatin inhibited tube formation and caused a 90% inhibition of total tube length (Fig. 8A and Fig. B). This effect was specific for cells transfected with angiomotin, whereas angiostatin did not affect tubulogenesis in control cells.


Angiomotin: an angiostatin binding protein that regulates endothelial cell migration and tube formation.

Troyanovsky B, Levchenko T, Månsson G, Matvijenko O, Holmgren L - J. Cell Biol. (2001)

(A) Angiostatin inhibits tube formation of angiomotin-transfected cells plated on matrigel. MAE-vector and MAE-angiomotin transfected cells were pretreated with 5 μg/ml angiostatin for 16 h before trypsinization and plating on matrigel. Images show tube formation 16 h after seeding on matrigel (Bar, 130 μm). (B) Total tube length formed in the presence or absence of angiostatin. The data represent the average from three independent experiments (error bars = SD).
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Related In: Results  -  Collection

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Figure 8: (A) Angiostatin inhibits tube formation of angiomotin-transfected cells plated on matrigel. MAE-vector and MAE-angiomotin transfected cells were pretreated with 5 μg/ml angiostatin for 16 h before trypsinization and plating on matrigel. Images show tube formation 16 h after seeding on matrigel (Bar, 130 μm). (B) Total tube length formed in the presence or absence of angiostatin. The data represent the average from three independent experiments (error bars = SD).
Mentions: To further explore the role of angiomotin in mediating angiostatin inhibition of angiogenesis, we studied the effect of angiostatin on the formation of vascular structures in the matrigel tube formation assay. No detectable difference between angiomotin- and vector-transfected MAE cells in the capacity to form tubes in vitro could be detected (Fig. 8 A). However, pretreating the cells for 16 h with angiostatin inhibited tube formation and caused a 90% inhibition of total tube length (Fig. 8A and Fig. B). This effect was specific for cells transfected with angiomotin, whereas angiostatin did not affect tubulogenesis in control cells.

Bottom Line: 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.These findings indicate that angiostatin inhibits cell migration by interfering with angiomotin activity in endothelial cells.

View Article: PubMed Central - PubMed

Affiliation: Center for Genomics Research and Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 76 Stockholm, Sweden.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus