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上皮-间质可塑性在腹膜假黏液瘤中的作用:对局部治疗的启示

Role of Epithelial-Mesenchymal Plasticity in Pseudomyxoma Peritonei: Implications for Locoregional Treatments.

作者信息

Calabrò Maria Luisa, Lazzari Nayana, Rigotto Giulia, Tonello Marco, Sommariva Antonio

机构信息

Immunology and Molecular Oncology, Veneto Institute of Oncology IOV-IRCCS, I-35128 Padua, Italy.

Surgical Oncology of the Esophagus and Digestive Tract, Veneto Institute of Oncology IOV-IRCCS, I-35128 Padua, Italy.

出版信息

Int J Mol Sci. 2020 Nov 30;21(23):9120. doi: 10.3390/ijms21239120.

Abstract

The mechanisms by which neoplastic cells disseminate from the primary tumor to metastatic sites, so-called metastatic organotropism, remain poorly understood. Epithelial-mesenchymal transition (EMT) plays a role in cancer development and progression by converting static epithelial cells into the migratory and microenvironment-interacting mesenchymal cells, and by the modulation of chemoresistance and stemness of tumor cells. Several findings highlight that pathways involved in EMT and its reverse process (mesenchymal-epithelial transition, MET), now collectively called epithelial-mesenchymal plasticity (EMP), play a role in peritoneal metastases. So far, the relevance of factors linked to EMP in a unique peritoneal malignancy such as pseudomyxoma peritonei (PMP) has not been fully elucidated. In this review, we focus on the role of epithelial-mesenchymal dynamics in the metastatic process involving mucinous neoplastic dissemination in the peritoneum. In particular, we discuss the role of expression profiles and phenotypic transitions found in PMP in light of the recent concept of EMP. A better understanding of EMP-associated mechanisms driving peritoneal metastasis will help to provide a more targeted approach for PMP patients selected for locoregional interventions involving cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

摘要

肿瘤细胞从原发性肿瘤扩散至转移部位的机制,即所谓的转移器官趋向性,目前仍知之甚少。上皮-间质转化(EMT)通过将静止的上皮细胞转化为具有迁移能力且能与微环境相互作用的间质细胞,并调节肿瘤细胞的化疗耐药性和干性,在癌症的发生和发展中发挥作用。多项研究结果表明,参与EMT及其逆向过程(间质-上皮转化,MET)的信号通路,现统称为上皮-间质可塑性(EMP),在腹膜转移中发挥作用。到目前为止,与EMP相关的因素在诸如腹膜假黏液瘤(PMP)这种独特的腹膜恶性肿瘤中的相关性尚未完全阐明。在本综述中,我们重点关注上皮-间质动态变化在涉及腹膜黏液性肿瘤播散的转移过程中的作用。特别是,我们根据EMP的最新概念,讨论PMP中发现的表达谱和表型转变的作用。更好地理解驱动腹膜转移的EMP相关机制,将有助于为选择进行包括肿瘤细胞减灭术和腹腔内热灌注化疗在内的局部区域干预的PMP患者提供更具针对性的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1987/7731245/7b2b804c505f/ijms-21-09120-g001.jpg

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