Myoepithelial cells are a dynamic barrier to epithelial dissemination.
Myoepithelial cells are a dynamic barrier to epithelial dissemination.
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DOI：
10.1083/jcb.201802144
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发表时间：
2018-10-01
期刊：
影响因子：
--
通讯作者：
Ewald AJ
中科院分区：
文献类型：
--
作者：
Sirka OK;Shamir ER;Ewald AJ
肌上皮细胞共同作为一道动态屏障，阻止Twist1 + 腔上皮细胞以及腔型和基底型乳腺癌细胞的侵袭和扩散。屏障功能取决于肌上皮的数量以及肌上皮内的平滑肌收缩能力和细胞间黏附。
乳腺上皮由内层的腔上皮和周围的肌上皮细胞层组成。癌细胞出现在肌上皮之外即定义为浸润性乳腺癌，但肌上皮在浸润过程中的作用仍不清楚。我们开发了一种三维器官型培养试验，通过转移前转录因子Twist1的谱系特异性表达来模拟这一过程。我们试图区分肌上皮在调节侵袭和局部扩散中的功能作用。肌上皮特异性Twist1表达诱导细胞自主性的肌上皮细胞逃逸。值得注意的是，腔上皮特异性Twist1表达很少足以导致逃逸。延时显微镜观察显示，肌上皮细胞共同抑制并重新内化入侵的Twist1 + 腔上皮细胞。屏障功能与肌上皮数量相关，并且需要α - 平滑肌肌动蛋白和P - 钙黏蛋白的表达。接下来我们证明了肌上皮细胞能够抑制和重新捕获浸润性癌细胞。我们的数据确立了肌上皮作为腔上皮扩散的动态屏障这一概念，并表明平滑肌收缩能力和细胞间黏附在屏障功能中起作用。
Myoepithelial cells function collectively as a dynamic barrier to the invasion and dissemination of Twist1+ luminal epithelial cells and both luminal and basal phenotype breast cancer cells. Barrier function depends on myoepithelial abundance and both smooth muscle contractility and intercellular adhesion within the myoepithelium. The mammary epithelium is composed of an inner luminal and surrounding myoepithelial cell layer. The presence of cancer cells beyond the myoepithelium defines invasive breast cancer, yet the role of the myoepithelium during invasion remains unclear. We developed a 3D organotypic culture assay to model this process through lineage-specific expression of the prometastatic transcription factor Twist1. We sought to distinguish the functional role of the myoepithelium in regulating invasion and local dissemination. Myoepithelial-specific Twist1 expression induced cell-autonomous myoepithelial cell escape. Remarkably, luminal-specific Twist1 expression was rarely sufficient for escape. Time-lapse microscopy revealed that myoepithelial cells collectively restrain and reinternalize invading Twist1+ luminal cells. Barrier function correlated with myoepithelial abundance and required the expression of α-smooth muscle actin and P-cadherin. We next demonstrated that myoepithelial cells can restrain and recapture invasive cancer cells. Our data establish the concept of the myoepithelium as a dynamic barrier to luminal dissemination and implicate both smooth muscle contractility and intercellular adhesion in barrier function.
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影响因子：
64.5
作者：
Cheung KJ;Gabrielson E;Werb Z;Ewald AJ
通讯作者：
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DOI：
10.1073/pnas.0901269106
发表时间：
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影响因子：
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作者：
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