Three Dimensional Cultures: A Tool To Study Normal Acinar Architecture vs. Malignant Transformation Of Breast Cells
Three Dimensional Cultures: A Tool To Study Normal Acinar Architecture vs. Malignant Transformation Of Breast Cells
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DOI：
10.3791/51311
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发表时间：
2014-04-01
影响因子：
1.2
通讯作者：
Kleer, Celina G.
中科院分区：
文献类型：
--
作者：
Pal, Anupama;Kleer, Celina G.
浸润性乳腺癌是一组以侵袭周围组织和转移为特征的恶性上皮性肿瘤。癌细胞和其微环境之间的信号相互作用对乳腺癌的生长和生物学行为产生了强大的影响(1)。然而，当细胞在二维培养(2D)中作为单层生长时，这些来自细胞外基质的信号大多丢失或它们的相关性未得到充分研究。近年来，在重建的基底膜上进行三维(3D)培养已成为一种重塑良性和恶性乳腺细胞组织结构的选择方法。3D培养的细胞保留了细胞外基质的重要线索，并提供了一个与生理相关的体外系统(2，3)。值得注意的是，越来越多的证据表明，与2D相比，细胞在3D中生长时的行为不同。3D培养可以有效地用于区分恶性表型和良性乳房表型，并支持所涉及的细胞和分子信号(3)。良性上皮细胞的特征之一是它们被极化，因此顶端细胞质朝向管腔，而基底质位于基底膜上。这种尖基两极在浸润性乳腺癌中消失，其特征是细胞解体，形成吻合和分支小管，随意地渗透到周围间质。这些良性腺癌和浸润性癌之间的组织病理学差异可以在3D(6，7)中再现。结合其他分子和细胞生物学技术，使用适当的读数，如单圆形腺泡结构的定量，或细胞增殖、极性和凋亡的有效分子标记的差异表达，3D培养可以为更好地了解细胞在恶性转化过程中的变化和描绘负责的信号提供重要工具。
Invasive breast carcinomas are a group of malignant epithelial tumors characterized by the invasion of adjacent tissues and propensity to metastasize. The interplay of signals between cancer cells and their microenvironment exerts a powerful influence on breast cancer growth and biological behavior(1). However, most of these signals from the extracellular matrix are lost or their relevance is understudied when cells are grown in two dimensional culture (2D) as a monolayer. In recent years, three dimensional (3D) culture on a reconstituted basement membrane has emerged as a method of choice to recapitulate the tissue architecture of benign and malignant breast cells. Cells grown in 3D retain the important cues from the extracellular matrix and provide a physiologically relevant ex vivo system(2,3). Of note, there is growing evidence suggesting that cells behave differently when grown in 3D as compared to 2D(4). 3D culture can be effectively used as a means to differentiate the malignant phenotype from the benign breast phenotype and for underpinning the cellular and molecular signaling involved(3). One of the distinguishing characteristics of benign epithelial cells is that they are polarized so that the apical cytoplasm is towards the lumen and the basal cytoplasm rests on the basement membrane. This apico-basal polarity is lost in invasive breast carcinomas, which are characterized by cellular disorganization and formation of anastomosing and branching tubules that haphazardly infiltrates the surrounding stroma. These histopathological differences between benign gland and invasive carcinoma can be reproduced in 3D(6,7). Using the appropriate read-outs like the quantitation of single round acinar structures, or differential expression of validated molecular markers for cell proliferation, polarity and apoptosis in combination with other molecular and cell biology techniques, 3D culture can provide an important tool to better understand the cellular changes during malignant transformation and for delineating the responsible signaling.