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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

MDA-MB-435, but not MCF-7, human carcinoma cells display functional coupling of S1 and αvβ3 integrins on VN. Depicted are phalloidin-stained cells 2 h after plating on wells coated with 10 μg/ml VN (top half of panels) or FN (bottom half) in plating medium alone or medium containing either 30 μg/ml mAb LM609, 25 μg/ml mAb 13, or 20 μM GST-mS1ED or -mS4ED. Bar, 50 μm.
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fig3: MDA-MB-435, but not MCF-7, human carcinoma cells display functional coupling of S1 and αvβ3 integrins on VN. Depicted are phalloidin-stained cells 2 h after plating on wells coated with 10 μg/ml VN (top half of panels) or FN (bottom half) in plating medium alone or medium containing either 30 μg/ml mAb LM609, 25 μg/ml mAb 13, or 20 μM GST-mS1ED or -mS4ED. Bar, 50 μm.

Mentions: To test if αvβ3 integrin activation on an ECM ligand is also functionally coupled to S1, MDA-MB-435 and MCF-7 cells were plated on either VN or FN (Fig. 3). MDA-MB-435 cells spread on VN and require αvβ3 integrins for this activity as spreading is blocked by mAb LM609. Although the MCF-7 cells spread on VN, this spreading is unaffected by LM609; these cells rely instead on αvβ1 integrins as spreading is blocked by either mAb 13 (Fig. 3) or αv-specific mAb M9 (de Vries et al., 1986). Neither cell type uses αvβ3 to respond to FN, rather both use α5β1 integrins that are blocked by either mAb 13 (Fig. 3) or mAb 16 (unpublished data).


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

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

MDA-MB-435, but not MCF-7, human carcinoma cells display functional coupling of S1 and αvβ3 integrins on VN. Depicted are phalloidin-stained cells 2 h after plating on wells coated with 10 μg/ml VN (top half of panels) or FN (bottom half) in plating medium alone or medium containing either 30 μg/ml mAb LM609, 25 μg/ml mAb 13, or 20 μM GST-mS1ED or -mS4ED. Bar, 50 μm.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: MDA-MB-435, but not MCF-7, human carcinoma cells display functional coupling of S1 and αvβ3 integrins on VN. Depicted are phalloidin-stained cells 2 h after plating on wells coated with 10 μg/ml VN (top half of panels) or FN (bottom half) in plating medium alone or medium containing either 30 μg/ml mAb LM609, 25 μg/ml mAb 13, or 20 μM GST-mS1ED or -mS4ED. Bar, 50 μm.
Mentions: To test if αvβ3 integrin activation on an ECM ligand is also functionally coupled to S1, MDA-MB-435 and MCF-7 cells were plated on either VN or FN (Fig. 3). MDA-MB-435 cells spread on VN and require αvβ3 integrins for this activity as spreading is blocked by mAb LM609. Although the MCF-7 cells spread on VN, this spreading is unaffected by LM609; these cells rely instead on αvβ1 integrins as spreading is blocked by either mAb 13 (Fig. 3) or αv-specific mAb M9 (de Vries et al., 1986). Neither cell type uses αvβ3 to respond to FN, rather both use α5β1 integrins that are blocked by either mAb 13 (Fig. 3) or mAb 16 (unpublished data).

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