Rapanotti Maria Cristina, Cugini Elisa, Scioli Maria Giovanna, Cenci Tonia, Anzillotti Silvia, Puzzuoli Martina, Terrinoni Alessandro, Ferlosio Amedeo, De Luca Anastasia, Orlandi Augusto
Anatomic Pathology, Department of Integrated Care Processes, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy.
Department of Laboratory Medicine, Tor Vergata University Hospital, 00133 Rome, Italy.
Int J Mol Sci. 2025 Apr 11;26(8):3617. doi: 10.3390/ijms26083617.
The atypical activation of the epithelial-to-mesenchymal transition represents one of the main mechanisms driving cancer cell dissemination. It enables epithelial cancer cells to detach from the primary tumor mass and gain survival advantages in the bloodstream, significantly contributing to the spread of circulating tumor cells. Notably, epithelial-to-mesenchymal transition is not a binary process but rather leads to the formation of a wide range of cell subpopulations characterized by the simultaneous expression of both epithelial and mesenchymal markers. Therefore, analyzing the modulation of EMT hallmarks during the conversion from healthy cells to metastatic cancer cells, which acquire stem mesenchymal characteristics, is of particular interest. This study investigates the expression of a panel of epithelial-to-mesenchymal transition-related genes in healthy cells, primary and metastatic cancer cells, and in mesenchymal cell lines, derived from various tissues, including the lung, colon, pancreas, skin, and neuro-ectoderm, with the aim of identifying potential cut-off values for assessing cancer aggressiveness. Interestingly, we found that the expression levels of , which encodes the epithelial marker E-cadherin, , encoding vascular endothelial cadherin, and the epithelial-to-mesenchymal transition-transcription factor , effectively distinguished primary from metastatic cancer cells. Additionally, our data suggest a tissue-specific signature in the modulation of epithelial-to-mesenchymal transition markers during cancer progression. Overall, our results underscore the importance of investigating epithelial-to-mesenchymal transition as a tissue-specific process to identify the most suitable markers acting as potential indicators of disease aggressiveness and therapeutic responsiveness.
上皮-间质转化的非典型激活是驱动癌细胞扩散的主要机制之一。它使上皮癌细胞能够从原发性肿瘤块脱离，并在血液中获得生存优势，显著促进循环肿瘤细胞的扩散。值得注意的是，上皮-间质转化不是一个二元过程，而是导致形成广泛的细胞亚群，其特征是同时表达上皮和间质标志物。因此，分析从健康细胞向获得干细胞间质特征的转移性癌细胞转化过程中上皮-间质转化特征的调控尤为重要。本研究调查了一组上皮-间质转化相关基因在健康细胞、原发性和转移性癌细胞以及来自各种组织（包括肺、结肠、胰腺、皮肤和神经外胚层）的间质细胞系中的表达，目的是确定评估癌症侵袭性的潜在临界值。有趣的是，我们发现编码上皮标志物E-钙黏蛋白的 、编码血管内皮钙黏蛋白的 以及上皮-间质转化转录因子 的表达水平有效地将原发性癌细胞与转移性癌细胞区分开来。此外，我们的数据表明在癌症进展过程中上皮-间质转化标志物的调控存在组织特异性特征。总体而言，我们的结果强调了将上皮-间质转化作为一个组织特异性过程进行研究的重要性，以确定最适合作为疾病侵袭性和治疗反应性潜在指标的标志物。
