MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, Gower Street, London, WC1E 6BT, United Kingdom.
Int J Biochem Cell Biol. 2011 Apr;43(4):496-503. doi: 10.1016/j.biocel.2010.12.019. Epub 2010 Dec 25.
During the initial stages of carcinogenesis, neoplastic transformation occurs in single epithelial cells and the transformed cells proliferate while being surrounded by normal epithelia. In Drosophila, normal and transformed epithelial cells compete with each other for survival, a process called cell competition. However, it was not known whether comparable phenomena also occur in mammals. Recently, several reports have shown that the interaction between normal and transformed epithelial cells causes various phenomena in mammals. For example, with elaborate cell culture systems that express oncoproteins or knockdown tumour suppressor proteins in an inducible manner, certain types of transformed cells have been shown to be apically eliminated from normal epithelial layers in an apoptosis-dependent or -independent manner. During the process of apical extrusion, various signalling pathways are modulated in transformed cells located within the normal epithelium, indicating that the presence of surrounding normal epithelial cells affects the behaviour and fate of transformed cells. Recent studies in mice have also shown that normal and transformed cells can compete with each other for survival during several processes such as liver regeneration. In this review, we will introduce these recent publications on interactions between normal and transformed mammalian epithelial cells. Furthermore, we will discuss how these studies can potentially lead to identification of biomarkers for precancerous cells and to invention of novel types of cancer prevention and treatment.
在癌变的初始阶段，肿瘤转化发生在单个上皮细胞中，转化细胞在正常上皮细胞的包围下增殖。在果蝇中，正常和转化的上皮细胞为了生存而相互竞争，这个过程称为细胞竞争。然而，在哺乳动物中是否也存在类似的现象尚不清楚。最近，有几项研究表明，正常和转化上皮细胞之间的相互作用在哺乳动物中会引起各种现象。例如，通过精心设计的细胞培养系统，以诱导的方式表达癌蛋白或敲低肿瘤抑制蛋白，已经证明某些类型的转化细胞可以以凋亡依赖或非依赖的方式从正常上皮层的顶端被消除。在顶端挤出的过程中，位于正常上皮内的转化细胞中的各种信号通路被调节，表明周围正常上皮细胞的存在会影响转化细胞的行为和命运。最近在小鼠中的研究也表明，在肝脏再生等多个过程中，正常和转化细胞可以相互竞争以获得生存。在这篇综述中，我们将介绍这些关于正常和转化的哺乳动物上皮细胞之间相互作用的最新出版物。此外，我们将讨论这些研究如何有助于确定癌前细胞的生物标志物，并发明新型的癌症预防和治疗方法。
