Lazard D, Sastre X, Frid M G, Glukhova M A, Thiery J P, Koteliansky V E
Laboratoire de Physiopathologie du Developpement, Centre National de la Recherche Scientifique Unité Associée 1337, Paris, France.
Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):999-1003. doi: 10.1073/pnas.90.3.999.
The expression of several differentiation markers in normal human mammary gland myoepithelium and in certain stromal fibroblasts ("myofibroblasts") associated with breast carcinomas was studied by immunofluorescence microscopy of frozen sections. Several antibodies to smooth muscle-specific proteins (smooth muscle alpha-actin, smooth muscle myosin heavy chains, calponin, alpha 1-integrin, and high molecular weight caldesmon) and to epithelial-specific proteins (cytokeratins, E-cadherin, and desmoplakin) were used to show that myoepithelial cells concomitantly express epithelial and smooth muscle markers whereas adjacent luminal cells express only epithelial markers. The same antibodies were used to establish that stromal myofibroblasts exhibit smooth muscle phenotypic properties characterized by the expression of all the smooth muscle markers examined except for high molecular weight caldesmon. In addition, both myoepithelium and myofibroblasts show a significant degree of heterogeneity in smooth muscle protein expression. Thus, myoepithelial cells and stromal myofibroblasts are epithelial and mesenchymal cells, respectively, which coordinately express a set of smooth muscle markers while maintaining their specific original features. The dual nature of myoepithelial cells and the phenotypic transition of fibroblasts to myofibroblasts are examples of the plasticity of the differentiated cell phenotype.
通过对冰冻切片进行免疫荧光显微镜检查,研究了几种分化标志物在正常人类乳腺肌上皮细胞以及与乳腺癌相关的某些基质成纤维细胞(“肌成纤维细胞”)中的表达情况。使用了几种针对平滑肌特异性蛋白(平滑肌α-肌动蛋白、平滑肌肌球蛋白重链、钙调蛋白、α1整合素和高分子量钙调蛋白)和上皮特异性蛋白(细胞角蛋白、E-钙黏蛋白和桥粒斑蛋白)的抗体,结果显示肌上皮细胞同时表达上皮标志物和平滑肌标志物,而相邻的管腔细胞仅表达上皮标志物。使用相同的抗体确定基质肌成纤维细胞表现出平滑肌表型特性,其特征在于除高分子量钙调蛋白外,所检测的所有平滑肌标志物均有表达。此外,肌上皮细胞和肌成纤维细胞在平滑肌蛋白表达方面均表现出显著的异质性。因此,肌上皮细胞和基质肌成纤维细胞分别为上皮细胞和间充质细胞,它们在维持其特定原始特征的同时协调表达一组平滑肌标志物。肌上皮细胞的双重性质以及成纤维细胞向肌成纤维细胞的表型转变是分化细胞表型可塑性的实例。