Hollier Brett G, Evans Kurt, Mani Sendurai A
Department of Molecular Pathology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77054, USA.
J Mammary Gland Biol Neoplasia. 2009 Mar;14(1):29-43. doi: 10.1007/s10911-009-9110-3. Epub 2009 Feb 26.
During cancer progression, some cells within the primary tumor may reactivate a latent embryonic program known as epithelial-to-mesenchymal transition (EMT). Through EMT, transformed epithelial cells can acquire the mesenchymal traits that seem to facilitate metastasis. Indeed, there is accumulating evidence that EMT and mesenchymal-related gene expression are associated with aggressive breast cancer subtypes and poor clinical outcome in breast cancer patients. More recently, the EMT program was shown to endow normal and transformed mammary epithelial cells with stem cell properties, including the ability to self-renew and efficiently initiate tumors. This link between EMT and stem cells may have numerous implications in the progression of breast tumors. The EMT process may facilitate the generation of cancer cells with the mesenchymal traits needed for dissemination as well as the self-renewal properties needed for initiation of secondary tumors. Breast cancer stem cells are resistant to many conventional cancer therapies, which can promote tumor relapse. Therefore, the generation of cancer stem cells by EMT may promote the development of refractory and resistant breast tumors. The purpose of this review is to summarize the findings related to EMT and stem cells in cancer progression and therapy resistance.
在癌症进展过程中,原发肿瘤内的一些细胞可能会重新激活一种称为上皮-间质转化(EMT)的潜在胚胎程序。通过EMT,转化的上皮细胞可以获得似乎有助于转移的间质特征。事实上,越来越多的证据表明,EMT和间质相关基因表达与侵袭性乳腺癌亚型以及乳腺癌患者的不良临床结局有关。最近,EMT程序被证明赋予正常和转化的乳腺上皮细胞干细胞特性,包括自我更新和有效启动肿瘤的能力。EMT与干细胞之间的这种联系可能对乳腺肿瘤的进展产生诸多影响。EMT过程可能有助于产生具有播散所需间质特征以及启动继发性肿瘤所需自我更新特性的癌细胞。乳腺癌干细胞对许多传统癌症疗法具有抗性,这可能会促进肿瘤复发。因此,通过EMT产生癌症干细胞可能会促进难治性和抗性乳腺肿瘤的发展。本综述的目的是总结与癌症进展和治疗抗性中EMT和干细胞相关的研究结果。