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恶性胸膜间皮瘤中的细胞外基质机械调节

ECM Mechanoregulation in Malignant Pleural Mesothelioma.

作者信息

Panzetta Valeria, Musella Ida, Fusco Sabato, Netti Paolo A

机构信息

Department of Chemical, Materials and Production Engineering, University of Naples Federico II, Naples, Italy.

Centro di Ricerca Interdipartimentale sui Biomateriali CRIB, University of Naples Federico II, Naples, Italy.

出版信息

Front Bioeng Biotechnol. 2022 Feb 14;10:797900. doi: 10.3389/fbioe.2022.797900. eCollection 2022.

Abstract

Malignant pleural mesothelioma is a relatively rare, but devastating tumor, because of the difficulties in providing early diagnosis and effective treatments with conventional chemo- and radiotherapies. Patients usually present pleural effusions that can be used for diagnostic purposes by cytological analysis. This effusion cytology may take weeks or months to establish and has a limited sensitivity (30%-60%). Then, it is becoming increasingly urgent to develop alternative investigative methods to support the diagnosis of mesothelioma at an early stage when this cancer can be treated successfully. To this purpose, mechanobiology provides novel perspectives into the study of tumor onset and progression and new diagnostic tools for the mechanical characterization of tumor tissues. Here, we report a mechanical and biophysical characterization of malignant pleural mesothelioma cells as additional support to the diagnosis of pleural effusions. In particular, we examined a normal mesothelial cell line (Met5A) and two epithelioid mesothelioma cell lines (REN and MPP89), investigating how malignant transformation can influence cellular function like proliferation, cell migration, and cell spreading area with respect to the normal ones. These alterations also correlated with variations in cytoskeletal mechanical properties that, in turn, were measured on substrates mimicking the stiffness of patho-physiological ECM.

摘要

恶性胸膜间皮瘤是一种相对罕见但极具破坏性的肿瘤,原因在于传统化疗和放疗在早期诊断和有效治疗方面存在困难。患者通常会出现胸腔积液,可通过细胞学分析用于诊断目的。这种积液细胞学检查可能需要数周或数月才能确定,且敏感性有限(30%-60%)。因此,开发替代的检测方法以在癌症可成功治疗的早期阶段辅助间皮瘤的诊断变得越来越紧迫。为此,机械生物学为肿瘤发生和进展的研究提供了新的视角,并为肿瘤组织的力学特性提供了新的诊断工具。在此,我们报告恶性胸膜间皮瘤细胞的力学和生物物理特性,作为对胸腔积液诊断的额外支持。特别是,我们研究了一种正常间皮细胞系(Met5A)和两种上皮样间皮瘤细胞系(REN和MPP89),探讨恶性转化相对于正常细胞如何影响细胞功能,如增殖、细胞迁移和细胞铺展面积。这些改变还与细胞骨架力学特性的变化相关,而细胞骨架力学特性又是在模拟病理生理细胞外基质硬度的底物上测量的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc13/8883334/6924213a32ad/fbioe-10-797900-g001.jpg

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