Physiology and Biophysics Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
Urol Oncol. 2010 Sep-Oct;28(5):534-40. doi: 10.1016/j.urolonc.2009.03.018. Epub 2009 May 17.
The epithelial-mesenchymal transition (EMT) is considered a key step in tumor progression, where the invasive cancer cells change from epithelial to mesenchymal phenotype. During this process, a decrease or loss in adhesion molecules expression and an increase in migration molecules expression are observed. The aim of this work was to determine the expression and cellular distribution of syndecan-1 and -2 (migration molecules) and E-cadherin and beta-catenin (adhesion molecules) in different stages of prostate cancer progression. A quantitative immunohistochemical study of these molecules was carried out in tissue samples from benign prostatic hyperplasia and prostate carcinoma, with low and high Gleason score, obtained from biopsies archives of the Clinic Hospital of the University of Chile and Dipreca Hospital. Polyclonal specific antibodies and amplification system of estreptavidin-biotin peroxidase and diaminobenzidine were used. Syndecan-1 was uniformly expressed in basolateral membranes of normal epithelium, changing to a granular cytoplasmatic expression pattern in carcinomas. Syndecan-2 was observed mainly in a cytoplasmatic granular pattern, with high immunostaining intensity in areas of low Gleason score. E-cadherin was detected in basolateral membrane of normal epithelia showing decreased expression in high Gleason score samples. beta-Catenin was found in cell membranes of normal epithelia changing its distribution toward the nucleus and cytoplasm in carcinoma samples. We concluded that changes in expression and cell distribution of E-cadherin and beta-catenin correlated with the progression degree of prostate adenocarcinoma, suggesting a role of these molecules as markers of progression and prognosis. Furthermore, changes in the pattern expression of syndecan-1 and -2 indicate that both molecules may be involved in the EMT and tumor progression of prostate cancer.
上皮-间充质转化(EMT)被认为是肿瘤进展的关键步骤,在此过程中,侵袭性癌细胞从上皮表型转变为间充质表型。在此过程中,观察到粘附分子表达的减少或丧失和迁移分子表达的增加。本工作的目的是确定在前列腺癌进展的不同阶段中,连接蛋白-1 和 -2(迁移分子)和 E-钙粘蛋白和β-连环蛋白(粘附分子)的表达和细胞分布。在来自智利大学临床医院和 Dipreca 医院活检档案的良性前列腺增生和前列腺癌组织样本中,进行了这些分子的定量免疫组织化学研究,这些样本具有低和高 Gleason 评分。使用了多克隆特异性抗体和链霉亲和素-生物素过氧化物酶扩增系统和二氨基联苯胺。连接蛋白-1 在正常上皮的基底外侧膜中均匀表达,在癌中变为颗粒细胞质表达模式。连接蛋白-2 主要观察到细胞质颗粒模式,在低 Gleason 评分区域具有高免疫染色强度。E-钙粘蛋白在正常上皮的基底外侧膜中检测到,在高 Gleason 评分样本中表达减少。β-连环蛋白位于正常上皮细胞的细胞膜中,在癌样本中其分布向核和细胞质改变。我们得出结论,E-钙粘蛋白和β-连环蛋白的表达和细胞分布的变化与前列腺腺癌的进展程度相关,表明这些分子作为进展和预后的标志物的作用。此外,连接蛋白-1 和 -2 的表达模式变化表明这两种分子可能参与前列腺癌的 EMT 和肿瘤进展。