Warburton M J, Ferns S A, Hughes C M, Sear C H, Rudland P S
J Natl Cancer Inst. 1987 Jun;78(6):1191-201.
Epithelial cell lines isolated from benign rat mammary tumors converted to elongated cells that showed some aspects of myoepithelial differentiation. This cellular conversion was blocked in cells isolated from malignant tumors. For investigation of the pathway of the conversion, a rat mammary epithelial cell line (Rama 25) that converted to elongated cells through a series of morphologically distinct intermediates was isolated. These intermediates formed a series in the order: Rama 25, Rama 25-I2, Rama 25-I1, Rama 25-I4, and elongated cells. These cell lines were examined for aspects of myoepithelial or mesenchymal differentiation with the use of a polyclonal antibody to type IV collagen and a keratin monoclonal antibody, LP34 (myoepithelial markers), or a polyclonal antibody to type I procollagen (mesenchymal marker) for cells grown on plastic or as tumors in nude mice. The more epithelial-like cell lines Rama 25 and Rama 25-I2 produced relatively small amounts of type IV collagen and did not stain with LP34 or anti-type I procollagen. The flatter, polygonal cell line Rama 25-I1 stained more strongly with the antibody to type IV collagen but did not stain with anti-type I procollagen. Rama 25-I1 cells, and to a lesser extent Rama 25-I4 cells in tumors, contained a network of cytoplasmic filaments that stained strongly with LP34. The elongated cells, Rama 25-I4 and Rama 25-floaters (Rama 25-FL), did not stain with LP34 in vitro but produced an extracellular matrix that stained with antibodies to both type I procollagen and type IV collagen. The results obtained with these marker proteins suggested that, in this series of morphologic intermediates, the myoepithelial phenotype was best expressed in Rama 25-I1 cells and to a lesser extent in 25-I4 cells. However, this phenotype was relatively unstable, converting to elongated cells, some of which have decreased myoepithelial and increased mesenchymal characteristics. Such a pathway may explain the mixed population of cells seen in some types of benign mammary tumor.
从良性大鼠乳腺肿瘤中分离出的上皮细胞系转变为细长细胞，这些细胞表现出一些肌上皮分化的特征。这种细胞转变在从恶性肿瘤中分离出的细胞中受到阻断。为了研究这种转变的途径，分离出了一种大鼠乳腺上皮细胞系（Rama 25），它通过一系列形态上不同的中间体转变为细长细胞。这些中间体按以下顺序形成一个系列：Rama 25、Rama 25-I2、Rama 25-I1、Rama 25-I4和细长细胞。使用针对IV型胶原的多克隆抗体和角蛋白单克隆抗体LP34（肌上皮标志物），或针对I型前胶原的多克隆抗体（间充质标志物），对在塑料上生长或在裸鼠体内形成肿瘤的这些细胞系进行肌上皮或间充质分化方面的检测。更像上皮细胞的细胞系Rama 25和Rama 25-I2产生相对少量的IV型胶原，并且不被LP34或抗I型前胶原染色。更扁平的多边形细胞系Rama 25-I1用针对IV型胶原的抗体染色更强，但不被抗I型前胶原染色。Rama 25-I1细胞，以及肿瘤中程度较轻的Rama 25-I4细胞，含有一个用LP34强烈染色的细胞质细丝网络。细长细胞Rama 25-I4和Rama 25-漂浮细胞（Rama 25-FL）在体外不被LP34染色，但产生一种用针对I型前胶原和IV型胶原的抗体染色的细胞外基质。用这些标志物蛋白获得的结果表明，在这一系列形态学中间体中，肌上皮表型在Rama 25-I1细胞中表达最佳，在25-I4细胞中表达程度较轻。然而，这种表型相对不稳定，会转变为细长细胞，其中一些细胞的肌上皮特征减少，间充质特征增加。这样一种途径可能解释了在某些类型的良性乳腺肿瘤中看到的混合细胞群体。
