Reversible transition towards a fibroblastic phenotype in a rat carcinoma cell line
Reversible transition towards a fibroblastic phenotype in a rat carcinoma cell line
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大鼠癌细胞系向成纤维细胞表型的可逆转变
DOI：
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
J. Thiery
中科院分区：
文献类型：
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作者：
B. Boyer;G. C. Tucker;A. Vallés;J. Gavrilovic;J. Thiery
关于细胞间粘附和细胞运动，检查了NBT-II细胞系的膀胱癌细胞从体外重建的上皮片解离和迁移的两种不同机制。通过2种不同的培养方案促进NBT-II膀胱癌细胞系的分散：（i）细胞外基质的一些组分沉积在培养基质（玻璃或塑料）上诱导癌细胞上皮片层的细胞分散，以及（ii）向培养基中添加Ultroser G（一种血清替代品）诱导NBT-II细胞的分散和运动性的获得。在两种培养条件下，NBT-II细胞解离，失去上皮形态，获得成纤维细胞形状并主动迁移。我们发现，在不同的细胞外基质蛋白中，只有胶原蛋白能够促进向成纤维细胞表型的转变（称为上皮向间充质转变或EMT）。此外，胶原蛋白的天然三维螺旋结构是其功能所必需的。在用Ultroser G诱导NBT-II细胞EMT期间，上皮细胞之间的连接分裂，极化上皮细胞组织丢失，所得单个细胞变得能动并呈现梭形成纤维细胞样外观。使用免疫荧光显微镜技术，我们证明，这种变化是伴随着桥粒斑块蛋白（桥粒斑蛋白，桥粒芯蛋白，斑珠蛋白）的重新分布和重组的细胞角蛋白和肌动蛋白胞衬蛋白丝系统。在成纤维细胞样细胞形式中重新形成波形蛋白类型的中等大小的细丝。通过从培养基中去除诱导因子，观察到的向成纤维细胞表型的转变（上皮向间充质转变或EMT）被完全逆转，如波形蛋白细丝的消失和新形成的上皮细胞中桥粒的再现所示。
Two distinct mechanisms by which bladder carcinoma cells of the NBT‐II cell line dissociate and migrate away from an in vitro reconstituted epithelial sheet were examined as regards intercellular adhesion and cell locomotion. Scattering of NBT‐II bladder carcinoma cell line was promoted by 2 distinct culture protocols: (i) deposition of some components of the extracellular matrix onto the culture substratum (glass or plastic) induced cell dispersion of the epithelial sheet of carcinoma cells, and (ii) addition of Ultroser G, a serum substitute, to the culture medium induced scattering and acquisition of motility of NBT‐II cells. Under both culture conditions, NBT‐II cells dissociated, lost their epithelial morphology, acquired fibroblastic shape and migrated actively. We show that, among different extracellular matrix proteins, only collagens were able to promote the transition towards fibroblastic phenotype (referred as epithelium‐to‐mesenchyme transition or EMT). Furthermore, the native 3‐dimensional helical structure of collagens was required for their function. During induction of EMT of NBT‐II cells with Ultroser G, the junctions between epithelial cells were split, polarized epithelial cell organization was lost, and the resulting individual cells became motile and assumed a spindle‐like fibroblastoid appearance. Using immunofluorescence microscopy techniques, we demonstrate that this change is accompanied by redistribution of desmosomal plaque proteins (desmoplakins, desmoglein, plakoglobin) and by reorganization of the cytokeratin and the actin‐fodrin filament systems. Intermediate‐sized filaments of the vimentin type were formed de novo in the fibroblastoid cell form. The observed transition towards fibroblastic phenotype (epithelium‐to‐mesenchyme transition or EMT) was fully reversed by removing the inducing factors from the culture medium, as shown by the disappearance of vimentin filaments and the reappearance of desmosomes in the newly formed epithelial cells.
肿瘤细胞不稳定、多样化和转移表型的进展：从癌基因到癌胎儿表达。
影响因子：
11.2
作者：
Nicolson,GL
通讯作者：
Nicolson,GL