Epithelial progenitor cell lines as models of normal, breast morphogenesis and neoplasia
Epithelial progenitor cell lines as models of normal, breast morphogenesis and neoplasia
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DOI：
10.1046/j.1365-2184.36.s.1.4.x
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发表时间：
2003-10-01
影响因子：
8.5
通讯作者：
Villadsen, R
中科院分区：
文献类型：
--
作者：
Petersen, OW;Gudjonsson, T;Villadsen, R
大多数人类乳腺癌表现出管腔特征，因此，很可能来自管腔上皮腔内的祖细胞。最近根据基因表达模式将其细分为至少三个管腔亚型。了解单个肿瘤的细胞起源的价值是明确的，应该有助于设计有效的治疗方法。然而，要做到这一点，我们需要一些策略来定义正常乳房中干细胞和祖细胞群体的性质。在这篇综述中，我们将讨论我们的技术方法来描绘上皮细胞类型的起源。一个重要的进步是通过应用基于谱系特异性表面抗原表达的免疫磁性细胞分选来纯化每种细胞类型。然后我们开发了化学定义的培养液，可以支持原代培养的腔上皮细胞或肌上皮细胞表型。在连续繁殖成功后，假设没有丢失标记，我们可以证明腔上皮细胞的一部分可以转化为肌上皮细胞，这意味着可能存在祖细胞群体。通过结合标志物表达和原位定位的信息，结合免疫磁性分选和随后的永生化，我们已经鉴定并分离出腔上皮室中一种细胞角蛋白19阳性的基底以上假定的前体细胞，并建立了具有代表性的细胞系。这种超基底来源的上皮细胞系能够产生自身和分化的腔上皮细胞和肌上皮细胞，此外，还能够在重组的基底膜内形成精细的末端导管小叶单位(TDLU)样结构。由于超过90%的乳腺癌发生在TDLU中，并且90%以上的细胞角蛋白19呈阳性，我们认为该细胞群包含乳腺癌前体细胞。
The majority of human breast carcinomas exhibit luminal characteristics and as such, are most probably derived from progenitor cells within the luminal epithelial compartment. This has been subdivided recently into at least three luminal subtypes based on gene expression patterns. The value of knowing the cellular origin of individual tumours is clear and should aid in designing effective therapies. To do this, however, we need strategies aimed at defining the nature of stem and progenitor cell populations in the normal breast. In this review, we will discuss our technical approach for delineating the origin of the epithelial cell types. A major step forward was the purification of each cell type by the application of immunomagnetic cell sorting based on expression of lineage-specific surface antigens. We then developed chemically defined media that could support either the luminal epithelial or the myoepithelial cell phenotype in primary cultures. Having succeeded in continuous propagation presumably without loss of markers, we could show that a subset of the luminal epithelial cells could convert to myoepithelial cells, signifying the possible existence of a progenitor cell population. By combining the information on marker expression and in situ localization with immunomagnetic sorting and subsequent immortalization, we have identifed and isolated a cytokeratin 19-positive suprabasal putative precursor cell in the luminal epithelial compartment and established representative cell lines. This suprabasal-derived epithelial cell line is able to generate both itself and differentiated luminal epithelial and myoepithelial cells, and in addition, is able to form elaborate terminal duct lobular unit (TDLU)-like structures within a reconstituted basement membrane. As more than 90% of breast cancers arise in TDLUs and more than 90% are also cytokeratin 19-positive, we suggest that this cell population contains a breast-cancer progenitor.