Sato H, Hasegawa T, Kanai Y, Tsutsumi Y, Osamura Y, Abe Y, Sakai H, Hirohashi S
Pathology Division, National Cancer Center Research Institue, Tokyo, Japan.
Virchows Arch. 2001 Jan;438(1):23-30. doi: 10.1007/s004280000318.
E-cadherin, the major intercellular adhesion molecule of epithelial cells, is important in determining the architecture of sarcomas, especially those showing epithelioid features. In addition to its role in cell adhesion, beta-catenin, a cadherin undercoat protein, has been shown to function as a downstream transcriptional activator of the Wnt/Wingless signaling pathway. In order to evaluate the significance of the cadherin cell adhesion system and the Wnt/Wingless signaling pathway in the morphogenesis and/or tumorigenesis of synovial sarcoma (a major type of sarcoma with epithelioid features), immunoreactivity for pan-cadherin, E-cadherin, and their undercoat proteins (alpha-, beta-,and gamma-catenins and p120) was evaluated in 15 synovial sarcomas. Immunoreactivity for pan-cadherin, E-cadherin, alpha-catenin, beta-catenin, and p120 was observed in all 15 specimens. Immunoreactivity for pan-cadherin was stronger than that for E-cadherin. Expression of gamma-catenin was detected in ten specimens. Although beta-catenin was observed only at the cell-cell boundaries in four specimens, it was present in the nucleus and cytoplasm and at the cell-cell boundaries in the other 11, suggesting constitutional activation of the Wnt/Wingless signaling pathway in synovial sarcoma. Direct sequencing for exon 3 of the beta-catenin gene, however, revealed no mutations in any of the 15 specimens. In conclusion, other types of cadherin besides E-cadherin, together with cadherin undercoat proteins, may play a role in cell adhesion in synovial sarcoma. Furthermore, mechanisms other than mutation of exon 3 of the beta-catenin gene may activate the Wnt/Wingless signaling pathway in this type of tumor.
E-钙黏蛋白是上皮细胞主要的细胞间黏附分子，在决定肉瘤的结构方面很重要，尤其是那些具有上皮样特征的肉瘤。β-连环蛋白作为一种钙黏蛋白的胞内附着蛋白，除了在细胞黏附中发挥作用外，还被证明可作为Wnt/Wingless信号通路的下游转录激活因子。为了评估钙黏蛋白细胞黏附系统和Wnt/Wingless信号通路在滑膜肉瘤（一种具有上皮样特征的主要肉瘤类型）的形态发生和/或肿瘤发生中的意义，对15例滑膜肉瘤进行了全钙黏蛋白、E-钙黏蛋白及其胞内附着蛋白（α-、β-和γ-连环蛋白以及p120）的免疫反应性评估。在所有15个标本中均观察到全钙黏蛋白、E-钙黏蛋白、α-连环蛋白、β-连环蛋白和p120的免疫反应性。全钙黏蛋白的免疫反应性强于E-钙黏蛋白。在10个标本中检测到γ-连环蛋白的表达。虽然仅在4个标本的细胞-细胞边界处观察到β-连环蛋白，但在其他11个标本中它存在于细胞核、细胞质以及细胞-细胞边界处，提示滑膜肉瘤中Wnt/Wingless信号通路的组成性激活。然而，对β-连环蛋白基因第3外显子的直接测序显示，15个标本中均未发现突变。总之，除E-钙黏蛋白外的其他类型钙黏蛋白以及钙黏蛋白胞内附着蛋白可能在滑膜肉瘤的细胞黏附中发挥作用。此外，除β-连环蛋白基因第3外显子突变外的其他机制可能激活这类肿瘤中的Wnt/Wingless信号通路。
