Three-dimensional culture of human breast epithelial cells: the how and the why.
Three-dimensional culture of human breast epithelial cells: the how and the why.
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DOI：
10.1007/978-1-62703-125-7_13
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Lelievre, Sophie A
中科院分区：
文献类型：
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作者：
Vidi, Pierre-Alexandre;Bissell, Mina J;Lelievre, Sophie A
器官是由不同类型的细胞有组织地组装而成的，这些细胞构成了功能分化所必需的结构。在具有外分泌功能的组织中，如乳腺，细胞-细胞和细胞-细胞外基质（ECM）相互作用建立了机制约束和复杂的生化信号网络，对腺上皮的分化和稳态至关重要。通过将上皮细胞置于三维（3D）培养条件下，乳腺已经优雅地获得了这些知识。三维细胞培养旨在概括正常和病理组织结构，从而为研究正常发育和疾病提供生理学相关模型。乳腺上皮的特殊结构由腺状结构（腺泡）组成，腺泡结构与分支导管系统相连。一层基顶极化的管腔细胞在顶极描绘导管或腺泡管腔。管腔细胞与肌上皮细胞接触，在基底极的某些区域，也与基底膜（BM）成分接触。在本章中，我们描述了这种精致的组织以及与癌症进展有关的混乱阶段如何在3D培养中重现。讨论了不同文化背景的优点和局限性。技术设计诱导表型调节，生化分析，并提出了最先进的成像。我们还解释了与传统的二维（2D）文化相比，信号在3D文化中的调节方式是如何不同的。我们相信，使用3D培养是一种不可或缺的方法来解开人类乳腺功能的复杂性，并将最好地服务于与乳腺癌的斗争。
Organs are made of the organized assembly of different cell types that contribute to the architecture necessary for functional differentiation. In those with exocrine function, such as the breast, cell–cell and cell–extracellular matrix (ECM) interactions establish mechanistic constraints and a complex biochemical signaling network essential for differentiation and homeostasis of the glandular epithelium. Such knowledge has been elegantly acquired for the mammary gland by placing epithelial cells under three-dimensional (3D) culture conditions. Three-dimensional cell culture aims at recapitulating normal and pathological tissue architectures, hence providing physiologically relevant models to study normal development and disease. The specific architecture of the breast epithelium consists of glandular structures (acini) connected to a branched ductal system. A single layer of basoapically polarized luminal cells delineates ductal or acinar lumena at the apical pole. Luminal cells make contact with myoepithelial cells and, in certain areas at the basal pole, also with basement membrane (BM) components. In this chapter, we describe how this exquisite organization as well as stages of disorganization pertaining to cancer progression can be reproduced in 3D cultures. Advantages and limitations of different culture settings are discussed. Technical designs for induction of phenotypic modulations, biochemical analyses, and state-of-the-art imaging are presented. We also explain how signaling is regulated differently in 3D cultures compared to traditional two-dimensional (2D) cultures. We believe that using 3D cultures is an indispensable method to unravel the intricacies of human mammary functions and would best serve the fight against breast cancer.