IJC：上皮间质转化与肿瘤转移

大量研究证实上皮-间质转化（EMT）是与癌症的侵袭和转移有牵连的关键事件。肿瘤细胞经过血液循环传播后，肿瘤细胞会发生间质上皮转化（MET），形成继发性的肿瘤转移灶。

然而，肿瘤细胞的这种形态学上的变化并没有从人类肿瘤标本组织中得到很有力的证据。在上皮癌组织中，上皮型细胞形态和基因表达在一定程度上得到了保留。虽然转化成间质型肿瘤细胞可能涉及许多癌症类型包括肉瘤，但在某些肿瘤中，分化成间质型的肿瘤细胞并不利于转移的发生发展。

事实上，有些类型的癌症细胞是通过上皮-间质转化以及间质上皮转化过程侵入周围组织并迁移，而不是通过淋巴管和血管发生转移。EMT的基因表达也与肿瘤组织学分级相关，而转录因子Snail、Slug和Twist传统上被认为是EMT的诱导因素，在一定条件下，他们也调解肿瘤细胞的去分化和维持干细胞状态。

在各种恶性肿瘤包括基底细胞样乳腺癌和大肠癌中上述基因经常不稳定，未分化型肿瘤细胞可用来预测早期转移扩散以及预后差。这项最新研究从临床角度讨论了一些肿瘤细胞分化和转移的争论，提出证据表明上皮型癌细胞在整个转移过程是一直维持其上皮型形态的。

编译自：Insights into cancer metastasis from a clinicopathologic perspective: Epithelial mesenchymal transition is not a necessary step

doi:10.1002/ijc.27745
PMC:
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Insights into cancer metastasis from a clinicopathologic perspective: Epithelial mesenchymal transition is not a necessary step

Michael Herman Chui*

Epithelial-mesenchymal transition (EMT) has been implicated as the critical event initiating cancer invasion and metastasis. After disseminating through the circulation, the malignant cells have been proposed to undergo subsequent mesenchymal-epithelial transition (MET) to form secondary tumours. However, strong evidence from human tumour specimens for this paradigm is lacking. In carcinomas, cancers derived from epithelial tissues, epithelial morphology and gene expression are almost always retained to some degree. While mesenchymal transdifferentiation may be involved in the pathogenesis of carcinosarcomas, even in these neoplasms, as well as in germ cell tumours capable of multi-lineage differentiation, the mesenchymal phenotype does not facilitate metastatic progression. Indeed, most cancers invade and travel through lymphatic and blood vessels via cohesive epithelial migration, rather than going through the EMT-MET sequence. EMT gene expression is also consistently associated with high histologic grade and while the transcription factors, Snail, Slug and Twist have traditionally been thought of as inducers of EMT, under certain conditions, they also mediate de-differentiation and maintenance of the stem cell state. In various malignancies, including basal-like breast cancer and colorectal cancer, the genetically unstable, undifferentiated phenotype predicts early metastatic spread and poor prognosis. This paper discusses some of the controversies surrounding differentiation and metastasis from a clinicopathologic perspective and presents evidence that the epithelial phenotype is maintained throughout the process of cancer metastasis.