Department of Oncology, University of Torino, 10126 Torino, Italy.
Interdepartmental Center for Studies on Asbestos and Other Toxic Particulates "G. Scansetti", University of Torino, 10126 Torino, Italy.
Int J Mol Sci. 2021 Nov 11;22(22):12216. doi: 10.3390/ijms222212216.
Malignant pleural mesothelioma (MPM) is an aggressive tumor mainly associated with asbestos exposure and is characterized by a very difficult pharmacological approach. One of the molecular mechanisms associated with cancer onset and invasiveness is the epithelial-to-mesenchymal transition (EMT), an event induced by different types of inducers, such as transforming growth factor β (TGFβ), the main inducer of EMT, and oxidative stress. MPM development and metastasis have been correlated to EMT; On one hand, EMT mediates the effects exerted by asbestos fibers in the mesothelium, particularly via increased oxidative stress and TGFβ levels evoked by asbestos exposure, thus promoting a malignant phenotype, and on the other hand, MPM acquires invasiveness via the EMT event, as shown by an upregulation of mesenchymal markers or, although indirectly, some miRNAs or non-coding RNAs, all demonstrated to be involved in cancer onset and metastasis. This review aims to better describe how EMT is involved in driving the development and invasiveness of MPM, in an attempt to open new scenarios that are useful in the identification of predictive markers and to improve the pharmacological approach against this aggressive cancer.
恶性胸膜间皮瘤(MPM)是一种主要与石棉暴露相关的侵袭性肿瘤,其药理学治疗方法极具挑战性。与癌症发生和侵袭性相关的分子机制之一是上皮-间充质转化(EMT),这是由不同类型的诱导剂诱导的事件,如转化生长因子β(TGFβ),EMT 的主要诱导剂,和氧化应激。MPM 的发展和转移与 EMT 有关;一方面,EMT 介导石棉纤维在间皮细胞中发挥的作用,特别是通过石棉暴露引起的氧化应激和 TGFβ水平的增加,从而促进恶性表型,另一方面,MPM 通过 EMT 事件获得侵袭性,如间充质标志物的上调,或者间接地,一些 miRNA 或非编码 RNA,所有这些都被证明与癌症的发生和转移有关。本综述旨在更好地描述 EMT 如何参与驱动 MPM 的发展和侵袭性,试图开辟新的场景,有助于识别预测标志物,并改善针对这种侵袭性癌症的药物治疗方法。