Syndecan-1 in breast cancer stroma fibroblasts regulates extracellular matrix fiber organization and carcinoma cell motility.
Syndecan-1 in breast cancer stroma fibroblasts regulates extracellular matrix fiber organization and carcinoma cell motility.
复制标题
乳腺癌基质成纤维细胞中的 Syndecan-1 调节细胞外基质纤维组织和癌细胞运动。
DOI：
10.1016/j.ajpath.2010.11.039
复制
发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Friedl,Andreas
中科院分区：
文献类型：
--
作者：
Yang,Ning;Mosher,Rachel;Seo,Songwon;Beebe,David;Friedl,Andreas
乳腺癌间质成纤维细胞常表达细胞表面蛋白多糖Syndecan-1(SDc1)。在人类乳腺癌样本中，间质Sdc1的表达与有组织的、平行的细胞外基质(ECM)纤维结构相关。为了研究基质Sdc1和纤维结构之间的可能联系，我们从Sdc1阳性和Sdc1阴性的小鼠和人乳腺成纤维细胞(分别称为ECM-Sdc1和ECM-mock)的培养中生成了具有生物活性的三维ECM。事实上，ECM-Sdc1显示出平行的纤维结构，这与ECM-MOCK的随机纤维排列形成了明显的对比。当乳腺癌细胞接种到无成纤维细胞的ECM中时，ECM-Sdc1而不是ECM-mock促进了它们的附着、侵袭和定向运动。我们进一步评估了ECM-Sdc1的结构/成分修饰对癌细胞行为的贡献。通过对培养表面的微接触打印，我们迫使Sdc1阴性的成纤维细胞产生平行纤维组织的ECM，模仿ECM-Sdc1中观察到的结构。我们发现，纤维形态决定了癌细胞迁移的方向性。相反，ECM-Sdc1中纤维连接蛋白水平的升高是导致乳腺癌细胞附着增强的原因。这些观察表明，乳腺癌间质成纤维细胞中Sdc1的表达促进了一种结构异常的ECM的组装，这种ECM允许乳腺癌的定向迁移和侵袭。
Stromal fibroblasts of breast carcinomas frequently express the cell surface proteoglycan syndecan-1 (Sdc1). In human breast carcinoma samples, stromal Sdc1 expression correlates with an organized, parallel, extracellular matrix (ECM) fiber architecture. To examine a possible link between stromal Sdc1 and the fiber architecture, we generated bioactive cell-free three-dimensional ECMs from cultures of Sdc1-positive and Sdc1-negative murine and human mammary fibroblasts (termed ECM-Sdc1 and ECM-mock, respectively). Indeed, ECM-Sdc1 showed a parallel fiber architecture that contrasted markedly with the random fiber arrangement of ECM-mock. When breast carcinoma cells were seeded into the fibroblast-free ECMs, ECM-Sdc1, but not ECM-mock, promoted their attachment, invasion, and directional movement. We further evaluated the contribution of the structural/compositional modifications in ECM-Sdc1 on carcinoma cell behavior. By microcontact printing of culture surfaces, we forced the Sdc1-negative fibroblasts to produce ECM with parallel fiber organization, mimicking the architecture observed in ECM-Sdc1. We found that the fiber topography governs carcinoma cell migration directionality. Conversely, an elevated fibronectin level in ECM-Sdc1 was responsible for the enhanced attachment of the breast carcinoma cells. These observations suggest that Sdc1 expression in breast carcinoma stromal fibroblasts promotes the assembly of an architecturally abnormal ECM that is permissive to breast carcinoma directional migration and invasion.