Gai Jin-Hong, Gong Peng-Tao, Li Jian-Hua, Man Yan-Gao, Ni Jin-Song, Ma Hongxi, Hao Fen-Yun, Zhang Xi-Chen, Liu Ying
Faculty of Veterinary Medicine, Gansu Agricultural University, Lanzhou, Gansu 730070;
Exp Ther Med. 2011 Jul;2(4):633-639. doi: 10.3892/etm.2011.251. Epub 2011 Apr 7.
Our previous studies showed that in patients with ductal carcinoma in situ (DCIS) of the breast, the tumor cells that overlie focal myoepithelial cell layer disruptions (FMCLDs) are generally arranged as finger-like projections that bud into the stroma. These budding cells have significantly more genetic instability and invasion-related gene expression, and less estrogen receptor (ER) expression, than their epithelial cell counterparts. This study aimed to assess these cells for potential molecular markers that are uniquely associated with cell adhesion and motility. Seventeen ER-positive DCIS cases were screened by immunostaining for ER, and 7 cases which harbored FMCLD lesions were used to examine the expression of the potential markers. Two cases with both DCIS and invasive lesions were selected for comparing the differences in molecular expression between these lesion types. The results showed that expression levels of talin, E-cadherin and focal adhesion kinase (FAK) in tumor cells overlying FMCLDs were higher than those within the corresponding duct. Integrin β1 staining was detected only in a small number of the tumor cells overlying the FMCLDs. Vinculin staining was weak (18%) or not detected (82%), and no expression was found in the tumor cells within the corresponding duct or in the pure isolated DCIS. By contrast, the expression levels of talin, vinculin and integrin β1 in the invasive tumors were distinctly higher than those in DCIS, and the expression of FAK and E-cadherin was lower. Using electron microscopy, we found that the tight junctions between tumor cells overlying the FMCLDs were reduced compared to the adjacent tumor cells in the lumen. These results indicate that the tumor cells overlying FMCLDs are likely to represent the specific precursors of invasive breast lesions. Our findings may also facilitate the identification of specific targets for further molecular profiling, which will more completely characterize this important cell population.
我们之前的研究表明，在乳腺导管原位癌（DCIS）患者中，覆盖局灶性肌上皮细胞层破坏（FMCLD）的肿瘤细胞通常呈指状突起排列，向基质中芽生。与上皮细胞对应物相比，这些芽生细胞具有明显更多的遗传不稳定性和侵袭相关基因表达，而雌激素受体（ER）表达较少。本研究旨在评估这些细胞是否存在与细胞黏附和运动性独特相关的潜在分子标志物。通过对ER进行免疫染色筛选出17例ER阳性DCIS病例，其中7例存在FMCLD病变，用于检测潜在标志物的表达。选择2例同时患有DCIS和浸润性病变的病例，比较这些病变类型之间分子表达的差异。结果显示，覆盖FMCLD的肿瘤细胞中，踝蛋白、E-钙黏蛋白和黏着斑激酶（FAK）的表达水平高于相应导管内的细胞。整合素β1染色仅在少数覆盖FMCLD的肿瘤细胞中检测到。纽蛋白染色较弱（18%）或未检测到（82%），在相应导管内的肿瘤细胞或纯孤立DCIS中未发现表达。相比之下，浸润性肿瘤中踝蛋白、纽蛋白和整合素β1的表达水平明显高于DCIS，而FAK和E-钙黏蛋白的表达较低。通过电子显微镜，我们发现覆盖FMCLD的肿瘤细胞之间的紧密连接比管腔内相邻肿瘤细胞减少。这些结果表明，覆盖FMCLD的肿瘤细胞可能代表浸润性乳腺病变的特定前体。我们的发现也可能有助于识别进一步分子分析的特定靶点，这将更全面地表征这一重要细胞群体。
