Syndecan-1-mediated cell spreading requires signaling by alphavbeta3 integrins in human breast carcinoma cells.
Syndecan-1-mediated cell spreading requires signaling by alphavbeta3 integrins in human breast carcinoma cells.
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发表时间：
2003
影响因子：
3.7
通讯作者：
DeannaLee M. Beauvais;A. Rapraeger
中科院分区：
文献类型：
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作者：
DeannaLee M. Beauvais;A. Rapraeger
多配体聚糖是在细胞粘附、增殖和分化中具有调节作用的细胞表面硫酸乙酰肝素蛋白聚糖[Annu. 68（1999）729]。虽然syndecan硫酸乙酰肝素链是必不可少的基质结合，少是已知的信号作用，其核心蛋白。为了模拟多配体蛋白聚糖特异性粘附，将MDA-MB-231乳腺癌细胞接种在针对多配体蛋白聚糖-4或多配体蛋白聚糖-1的抗体上。虽然细胞通过多配体蛋白聚糖-4粘附扩散，但细胞通过多配体蛋白聚糖-1粘附不扩散。然而，通过多配体蛋白聚糖-1粘附的细胞可以被Mn（2+）诱导扩散，这表明需要β（1）或β（3）整联蛋白伴侣的活化。令人惊讶的是，用功能激活β（1）抗体预处理细胞不会诱导扩散，而功能阻断β（1）整联蛋白抗体会诱导扩散，这表明涉及β（1）-β（3）整联蛋白的串扰。事实上，β（1）整联蛋白激活的阻断诱导α（v）β（3）整联蛋白激活，可通过可溶性纤维蛋白原结合检测。对多配体蛋白聚糖-1应答的扩散不依赖于整合素-配体结合。此外，与不破坏细胞粘附的可溶性鼠多配体蛋白聚糖-1胞外域的竞争仍然阻断了扩散机制。这些数据表明多配体蛋白聚糖-1核心蛋白的胞外域直接参与与α（v）β（3）整联蛋白协同信号传导的信号传导复合物的形成;通过该复合物的信号传导受到β（1）整联蛋白的负调控。
Syndecans are cell surface heparan sulfate proteoglycans with regulatory roles in cell adhesion, proliferation, and differentiation [Annu. Rev. Biochem. 68 (1999) 729]. While the syndecan heparan sulfate chains are essential for matrix binding, less is known about the signaling role of their core proteins. To mimic syndecan-specific adhesion, MDA-MB-231 mammary carcinoma cells were plated on antibodies against syndecan-4 or syndecan-1. While cells adherent via syndecan-4 spread, cells adherent via syndecan-1 do not. However, cells adherent via syndecan-1 can be induced to spread by Mn(2+), suggesting that activation of a beta(1) or beta(3) integrin partner is required. Surprisingly, pretreatment of cells with a function-activating beta(1) antibody does not induce spreading, whereas function-blocking beta(1) integrin antibodies do, suggesting involvement of a beta(1)-to-beta(3) integrin cross-talk. Indeed, blockade of beta(1) integrin activation induces alpha(v)beta(3) integrin activation detectable by soluble fibrinogen binding. Spreading in response to syndecan-1 is independent of integrin-ligand binding. Furthermore, competition with soluble murine syndecan-1 ectodomain, which does not disrupt cell adhesion, nonetheless blocks the spreading mechanism. These data suggest that the ectodomain of the syndecan-1 core protein directly participates in the formation of a signaling complex that signals in cooperation with alpha(v)beta(3) integrins; signaling via this complex is negatively regulated by beta(1) integrins.