Gotzmann Josef, Mikula Mario, Eger Andreas, Schulte-Hermann Rolf, Foisner Roland, Beug Hartmut, Mikulits Wolfgang
Institute of Cancer Research, University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
Mutat Res. 2004 Jan;566(1):9-20. doi: 10.1016/s1383-5742(03)00033-4.
Carcinomas arising from epithelial cells represent the most prevalent malignancies in humans, and metastasis is the major cause for the death of carcinoma patients. The breakdown of epithelial cell homeostasis leading to aggressive cancer progression has been correlated with the loss of epithelial characteristics and the acquisition of a migratory phenotype. This phenomenon, referred to as epithelial to mesenchymal transition (EMT), is considered as a crucial event in late stage tumorigenesis. Here we summarize the multitude of EMT models derived from different tissues, and review the diversity of molecular mechanisms contributing to the plasticity of epithelial cells. In particular, the synergism between activation of Ras, provided by the aberrant stimulation of receptor tyrosine kinases, and transforming growth factor (TGF)-beta signaling plays a pivotal role in inducing EMT of various epithelial cell types. Cytokines such as TGF-beta and extracellular matrix molecules are thought to fundamentally contribute to the microenvironmental interaction between stromal and malignant cells, and provide the basis for a broad repertoire of epithelial differentiation. Investigations of EMT tumor models, which represent in vitro correlates to local invasion and metastasis in vivo, facilitate the identification of diagnostic markers for a more accurate and faithful clinical and pathological assessment of epithelial tumors. In addition, the analysis of molecular mechanisms involved in EMT might yield novel therapeutic targets for the specific treatment of aggressive carcinomas.
上皮细胞来源的癌是人类最常见的恶性肿瘤，而转移是癌症患者死亡的主要原因。上皮细胞稳态的破坏导致侵袭性癌症进展，这与上皮特征的丧失和迁移表型的获得有关。这种现象，即上皮-间质转化（EMT），被认为是晚期肿瘤发生中的关键事件。在这里，我们总结了源自不同组织的多种EMT模型，并回顾了促成上皮细胞可塑性的分子机制的多样性。特别是，受体酪氨酸激酶的异常刺激所提供的Ras激活与转化生长因子（TGF）-β信号传导之间的协同作用，在诱导各种上皮细胞类型的EMT中起关键作用。诸如TGF-β等细胞因子和细胞外基质分子被认为从根本上促成了基质细胞与恶性细胞之间的微环境相互作用，并为广泛的上皮分化提供了基础。对EMT肿瘤模型的研究，其代表了体内局部侵袭和转移的体外相关情况，有助于识别诊断标志物，以便对上皮肿瘤进行更准确和可靠的临床及病理评估。此外，对EMT所涉及分子机制的分析可能会产生针对侵袭性癌的特异性治疗的新靶点。
