Verrill Clare, Cerundolo Lucia, Mckee Chad, White Michael, Kartsonaki Christiana, Fryer Eve, Morris Emma, Brewster Simon, Ratnayaka Indrika, Marsden Luke, Lilja Hans, Muschel Ruth, Lu Xin, Hamdy Freddie, Bryant Richard J
Department of Cellular Pathology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, UK.
Nuffield Department of Surgical Sciences, University of Oxford, Headington, Oxford, UK.
Oncotarget. 2016 Jan 12;7(2):1107-19. doi: 10.18632/oncotarget.6689.
Epithelial to mesenchymal transition (EMT) of cancer cells involves loss of epithelial polarity and adhesiveness, and gain of invasive and migratory mesenchymal behaviours. EMT occurs in prostate cancer (PCa) but it is unknown whether this is in specific areas of primary tumours. We examined whether any of eleven EMT-related proteins have altered expression or subcellular localisation within the extraprostatic extension component of locally advanced PCa compared with other localisations, and whether similar changes may occur in in vitro organotypic PCa cell cultures and in vivo PCa models. Expression profiles of three proteins (E-cadherin, Snail, and α-smooth muscle actin) were significantly different in extraprostatic extension PCa compared with intra-prostatic tumour, and 18/27 cases had an expression change of at least one of these three proteins. Of the three significantly altered EMT proteins in pT3 samples, one showed similar significantly altered expression patterns in in vitro organotypic culture models, and two in in vivo Pten-/- model samples. These results suggest that changes in EMT protein expression can be observed in the extraprostatic extension component of locally invasive PCa. The biology of some of these changes in protein expression may be studied in certain in vitro and in vivo PCa models.
癌细胞的上皮-间质转化（EMT）涉及上皮极性和黏附性的丧失，以及侵袭性和迁移性间质行为的获得。EMT在前列腺癌（PCa）中会发生，但尚不清楚这是否发生在原发性肿瘤的特定区域。我们研究了与其他定位相比，在局部晚期PCa的前列腺外扩展成分中，11种与EMT相关的蛋白质中是否有任何一种的表达或亚细胞定位发生了改变，以及在体外器官型PCa细胞培养和体内PCa模型中是否会发生类似的变化。与前列腺内肿瘤相比，前列腺外扩展PCa中三种蛋白质（E-钙黏蛋白、Snail和α-平滑肌肌动蛋白）的表达谱有显著差异，27例中有18例这三种蛋白质中至少有一种的表达发生了变化。在pT3样本中三种显著改变的EMT蛋白质中，一种在体外器官型培养模型中显示出类似的显著改变的表达模式，两种在体内Pten-/-模型样本中显示出类似的表达模式。这些结果表明，在局部侵袭性PCa的前列腺外扩展成分中可以观察到EMT蛋白质表达的变化。其中一些蛋白质表达变化的生物学特性可以在某些体外和体内PCa模型中进行研究。
