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The syndecan-1 ectodomain regulates alphavbeta3 integrin activity in human mammary carcinoma cells.

Beauvais DM, Burbach BJ, Rapraeger AC - J. Cell Biol. (2004)

Bottom Line: This paper demonstrates that the alpha(v)beta(3) integrin and syndecan-1 (S1) are functionally coupled.Coupling of the syndecan to alpha(v)beta(3) requires the S1 ectodomain (ED), as ectopic expression of glycosylphosphatidylinositol-linked S1ED enhances alpha(v)beta(3) recognition of vitronectin; and treatments that target this domain, including competition with recombinant S1ED protein or anti-S1ED antibodies, mutation of the S1ED, or down-regulation of S1 expression by small-interfering RNAs, disrupt alpha(v)beta(3)-dependent cell spreading and migration.Thus, S1 is likely to be a critical regulator of many cellular behaviors that depend on activated alpha(v)beta(3) integrins.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.

ABSTRACT
The alpha(v)beta(3) integrin participates in cell morphogenesis, growth factor signaling, and cell survival. Activation of the integrin is central to these processes and is influenced by specific ECM components, which engage both integrins and syndecans. This paper demonstrates that the alpha(v)beta(3) integrin and syndecan-1 (S1) are functionally coupled. The integrin is dependent on the syndecan to become activated and to mediate signals required for MDA-MB-231 and MDA-MB-435 human mammary carcinoma cell spreading on vitronectin or S1-specific antibody. Coupling of the syndecan to alpha(v)beta(3) requires the S1 ectodomain (ED), as ectopic expression of glycosylphosphatidylinositol-linked S1ED enhances alpha(v)beta(3) recognition of vitronectin; and treatments that target this domain, including competition with recombinant S1ED protein or anti-S1ED antibodies, mutation of the S1ED, or down-regulation of S1 expression by small-interfering RNAs, disrupt alpha(v)beta(3)-dependent cell spreading and migration. Thus, S1 is likely to be a critical regulator of many cellular behaviors that depend on activated alpha(v)beta(3) integrins.

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Related in: MedlinePlus

S1ED inhibitors disrupt αvβ3 integrin–dependent cell migration on VN. MDA-MB-231, MDA-MB-435, and MCF-7 cells in plating medium alone (black) or in plating medium containing either 20 μM GST-mS1ED (white) or 250 μg/ml mS1ED pAbs (gray) were seeded on polycarbonate filters coated with either 10 μg/ml VN (A) or FN (B) in a modified Boyden chamber. After 16 h, cells that migrated through the filter in response to 10% FBS in the lower chamber were quantified by colorimetric staining. The error bars represent the SEM from three independent experiments.
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fig5: S1ED inhibitors disrupt αvβ3 integrin–dependent cell migration on VN. MDA-MB-231, MDA-MB-435, and MCF-7 cells in plating medium alone (black) or in plating medium containing either 20 μM GST-mS1ED (white) or 250 μg/ml mS1ED pAbs (gray) were seeded on polycarbonate filters coated with either 10 μg/ml VN (A) or FN (B) in a modified Boyden chamber. After 16 h, cells that migrated through the filter in response to 10% FBS in the lower chamber were quantified by colorimetric staining. The error bars represent the SEM from three independent experiments.

Mentions: To test the role of the S1ED in αvβ3 integrin–dependent signaling in another functional assay, cells were examined for their ability to migrate across VN- or FN-coated filters in the presence or absence of S1ED pAb (250 μg/ml) or GST-mS1ED recombinant protein (20 μM). Migration of treated MDA-MB-231 and MB-435 cells across VN is suppressed two- to fourfold relative to untreated controls (Fig. 5 A). MCF-7 cell migration across VN, which is αvβ1 dependent, is unaffected by either treatment. Furthermore, neither inhibitor has any effect on cell migration across FN in any of the three cell types tested (Fig. 5 B).


The syndecan-1 ectodomain regulates alphavbeta3 integrin activity in human mammary carcinoma cells.

Beauvais DM, Burbach BJ, Rapraeger AC - J. Cell Biol. (2004)

S1ED inhibitors disrupt αvβ3 integrin–dependent cell migration on VN. MDA-MB-231, MDA-MB-435, and MCF-7 cells in plating medium alone (black) or in plating medium containing either 20 μM GST-mS1ED (white) or 250 μg/ml mS1ED pAbs (gray) were seeded on polycarbonate filters coated with either 10 μg/ml VN (A) or FN (B) in a modified Boyden chamber. After 16 h, cells that migrated through the filter in response to 10% FBS in the lower chamber were quantified by colorimetric staining. The error bars represent the SEM from three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172512&req=5

fig5: S1ED inhibitors disrupt αvβ3 integrin–dependent cell migration on VN. MDA-MB-231, MDA-MB-435, and MCF-7 cells in plating medium alone (black) or in plating medium containing either 20 μM GST-mS1ED (white) or 250 μg/ml mS1ED pAbs (gray) were seeded on polycarbonate filters coated with either 10 μg/ml VN (A) or FN (B) in a modified Boyden chamber. After 16 h, cells that migrated through the filter in response to 10% FBS in the lower chamber were quantified by colorimetric staining. The error bars represent the SEM from three independent experiments.
Mentions: To test the role of the S1ED in αvβ3 integrin–dependent signaling in another functional assay, cells were examined for their ability to migrate across VN- or FN-coated filters in the presence or absence of S1ED pAb (250 μg/ml) or GST-mS1ED recombinant protein (20 μM). Migration of treated MDA-MB-231 and MB-435 cells across VN is suppressed two- to fourfold relative to untreated controls (Fig. 5 A). MCF-7 cell migration across VN, which is αvβ1 dependent, is unaffected by either treatment. Furthermore, neither inhibitor has any effect on cell migration across FN in any of the three cell types tested (Fig. 5 B).

Bottom Line: This paper demonstrates that the alpha(v)beta(3) integrin and syndecan-1 (S1) are functionally coupled.Coupling of the syndecan to alpha(v)beta(3) requires the S1 ectodomain (ED), as ectopic expression of glycosylphosphatidylinositol-linked S1ED enhances alpha(v)beta(3) recognition of vitronectin; and treatments that target this domain, including competition with recombinant S1ED protein or anti-S1ED antibodies, mutation of the S1ED, or down-regulation of S1 expression by small-interfering RNAs, disrupt alpha(v)beta(3)-dependent cell spreading and migration.Thus, S1 is likely to be a critical regulator of many cellular behaviors that depend on activated alpha(v)beta(3) integrins.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.

ABSTRACT
The alpha(v)beta(3) integrin participates in cell morphogenesis, growth factor signaling, and cell survival. Activation of the integrin is central to these processes and is influenced by specific ECM components, which engage both integrins and syndecans. This paper demonstrates that the alpha(v)beta(3) integrin and syndecan-1 (S1) are functionally coupled. The integrin is dependent on the syndecan to become activated and to mediate signals required for MDA-MB-231 and MDA-MB-435 human mammary carcinoma cell spreading on vitronectin or S1-specific antibody. Coupling of the syndecan to alpha(v)beta(3) requires the S1 ectodomain (ED), as ectopic expression of glycosylphosphatidylinositol-linked S1ED enhances alpha(v)beta(3) recognition of vitronectin; and treatments that target this domain, including competition with recombinant S1ED protein or anti-S1ED antibodies, mutation of the S1ED, or down-regulation of S1 expression by small-interfering RNAs, disrupt alpha(v)beta(3)-dependent cell spreading and migration. Thus, S1 is likely to be a critical regulator of many cellular behaviors that depend on activated alpha(v)beta(3) integrins.

Show MeSH
Related in: MedlinePlus