Glukhova M, Koteliansky V, Sastre X, Thiery J P
Laboratory of Developmental Physiopathology, Curie Institute, Paris, France.
Am J Pathol. 1995 Mar;146(3):706-16.
To analyze the role of various elements of the adhesion system in the organization of the normal mammary gland and in breast carcinoma, we have studied simultaneously the expression of integrins, E- and P-cadherins, and cytoplasmic constituents of adherens junctions. In the normal gland, E-cadherin and alpha-catenin are present in luminal epithelial and myoepithelial cells, whereas integrins are more abundant in acinar epithelial and in myoepithelial cells. We demonstrate here that, in addition, myoepithelial cells express much more vinculin and alpha-actinin than luminal epithelial cells, whereas talin and focal adhesion kinase (pp125FAK) are restricted to the basal cell layer. In invasive carcinoma, E-cadherin is usually present although often in reduced amount; different integrin subunits are expressed either by a fraction or by all of the cells or are absent. However, the cytoplasmic components of adherens junctions, such as alpha-catenin, vinculin, alpha-actinin, talin, and pp125FAK, are expressed at low levels or cannot be detected in the carcinoma cells. Our data suggest that 1), in the normal mammary gland, the myoepithelial cells, being particularly rich in integrins and cytoplasmic components of the adherens junctions, play an important role in the maintenance of tissue integrity; 2), in invasive carcinoma, cell aggregates may be maintained due to varying levels of expression of E-cadherin and/or integrins; and 3), interaction of the transmembrane adhesion molecules with the cytoskeleton in carcinoma may be impaired as revealed by reduced levels of expression of alpha-catenin, vinculin, alpha-actinin, talin, and pp125FAK. Importantly, carcinoma cells, when exposed to stroma during invasion, do not acquire the adhesion apparatus characteristic of normal cells in contact with the extracellular matrix.
为分析黏附系统的各种成分在正常乳腺组织构成及乳腺癌中的作用，我们同时研究了整合素、E-钙黏蛋白和P-钙黏蛋白以及黏着连接的细胞质成分的表达情况。在正常乳腺组织中，E-钙黏蛋白和α-连环蛋白存在于管腔上皮细胞和肌上皮细胞中，而整合素在腺泡上皮细胞和肌上皮细胞中更为丰富。我们在此证明，此外，肌上皮细胞比管腔上皮细胞表达更多的纽蛋白和α-辅肌动蛋白，而踝蛋白和黏着斑激酶（pp125FAK）则局限于基底细胞层。在浸润性癌中，E-钙黏蛋白通常存在，尽管含量常常减少；不同的整合素亚基要么部分细胞表达，要么所有细胞都表达，要么缺失。然而，黏着连接的细胞质成分，如α-连环蛋白、纽蛋白、α-辅肌动蛋白、踝蛋白和pp125FAK，在癌细胞中表达水平较低或无法检测到。我们的数据表明：1）在正常乳腺组织中，肌上皮细胞富含整合素和黏着连接的细胞质成分，在维持组织完整性方面发挥重要作用；2）在浸润性癌中，由于E-钙黏蛋白和/或整合素表达水平的变化，细胞聚集体可能得以维持；3）如α-连环蛋白、纽蛋白、α-辅肌动蛋白、踝蛋白和pp125FAK表达水平降低所示，癌细胞中跨膜黏附分子与细胞骨架的相互作用可能受损。重要的是，癌细胞在侵袭过程中与基质接触时，不会获得与细胞外基质接触的正常细胞所特有的黏附装置。
