Am J Transl Res. 2010 Oct 23;3(1):90-9.
Prostate cancer (PCa) has a predilection to metastasize to bone. Before metastasis can occur there is transition of the sessile epithelial cancer cells to become motile and invasive mesenchymal phenotypes by an important albeit transient process called Epithelial-to-Mesenchymal Transition (EMT). The cascade of molecular events triggered by this process is clinically relevant as they are associated with cancer stem-like cells (CSC), decreased senescence and eventual drug resistance phenotype. We interrogated some EMT markers that have been implicated in primary and bone metastasis of PCa using archived patient samples. Using an immunohistochemical approach, E-cadherin, Vimentin, ZEB1, Notch-1, PDGF-D and NF-κB were analyzed. Cases were microscopically scored using intensity (0, +1, +2, +3) and percentage of positive cells. Data was statistically analyzed using Fisher's Exact Test. Aberrant expression of EMT markers E-cadherin, Vimentin, PDGF-D, NF-κB, Notch-1 and ZEB1 was observed in PCa (primary tumor specimen) and bone metastasis tissues. The aberrant expression pattern varied according to the location within the tumor with higher expression was observed more at the invasive tumor front (ITF) vs. the center of the tumor. Notch-1 was significantly over-expressed in bone metastasis compared to primary PCa (p=0.057). The expression levels, intensity and % of positive cells of the remaining markers were not statistically significant in PCa vs. bone metastasis. In conclusion, protein expression analysis revealed the existence of EMT phenotype in the PCa and bone metastasis. Variation in the aberrant expression patterns at the invasive tumor front indicates the role of EMT markers in tumor invasion. Our results suggest that Notch-1 could play a role in PCa bone metastasis. Studies in larger patient cohorts are warranted before these EMT molecular markers can be translated to the clinical use.
前列腺癌 (PCa) 倾向于转移至骨骼。在转移发生之前，静止的上皮癌细胞通过一个重要但短暂的过程转变为运动和侵袭的间充质表型，这个过程称为上皮-间充质转化 (EMT)。这个过程引发的分子事件级联与癌症干细胞样细胞 (CSC)、衰老减少和最终耐药表型有关，因此具有临床相关性。我们使用存档的患者样本研究了一些 EMT 标志物，这些标志物与 PCa 的原发性和骨转移有关。我们采用免疫组织化学方法分析了 E-钙黏蛋白、波形蛋白、ZEB1、Notch-1、PDGF-D 和 NF-κB。使用显微镜对每个病例进行强度（0、+1、+2、+3）和阳性细胞百分比评分。使用 Fisher 精确检验对数据进行统计学分析。在 PCa（原发性肿瘤标本）和骨转移组织中观察到 EMT 标志物 E-钙黏蛋白、波形蛋白、PDGF-D、NF-κB、Notch-1 和 ZEB1 的异常表达。异常表达模式根据肿瘤内的位置而变化，在侵袭性肿瘤前缘 (ITF) 观察到更高的表达，而在肿瘤中心则较低。与原发性 PCa 相比，Notch-1 在骨转移中显著过表达 (p=0.057)。在 PCa 与骨转移中，其余标志物的表达水平、强度和阳性细胞百分比均无统计学差异。总之，蛋白质表达分析显示 EMT 表型存在于 PCa 和骨转移中。在侵袭性肿瘤前缘的异常表达模式的变化表明 EMT 标志物在肿瘤侵袭中的作用。我们的结果表明 Notch-1 可能在 PCa 骨转移中发挥作用。在这些 EMT 分子标志物能够转化为临床应用之前，需要在更大的患者队列中进行研究。
