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药理学性初级纤毛紊乱在体外二维和三维恶性胸膜间皮瘤背景下的影响

Effects of pharmacological primary cilium disturbance in the context of in vitro 2D and 3D malignant pleura mesothelioma.

作者信息

Jagirdar Rajesh M, Pitaraki Eleanna, Kotsiou Ourania S, Rouka Erasmia, Sinis Sotirios I, Varsamas Charalampos, Marnas Periklis, Stergiopoulou Elpiniki, Giannou Anastasios, Hatzoglou Chrissi, Gourgoulianis Konstantinos I, Zarogiannis Sotirios G

机构信息

Department of Physiology, Faculty of Medicine, School of Health Sciences, University of Thessaly, BIOPOLIS, 41500, Larissa, Greece.

Department of Physiology, Faculty of Medicine, School of Health Sciences, University of Thessaly, BIOPOLIS, 41500, Larissa, Greece; Department of Human Pathophysiology, Faculty of Nursing, School of Health Sciences, University of Thessaly, GAIOPOLIS, 41500, Larissa, Greece.

出版信息

Biochem Biophys Res Commun. 2023 Apr 30;654:128-135. doi: 10.1016/j.bbrc.2023.03.011. Epub 2023 Mar 6.

DOI:10.1016/j.bbrc.2023.03.011
PMID:36907140
Abstract

INTRODUCTION

Primary cilium (PC) is a single non-motile antenna-like organelle composed of a microtubule core axon originating from the mother centriole of the centrosome. The PC is universal in all mammalian cells and protrudes to the extracellular environment receiving mechanochemical cues that it transmits in the cell.

AIM

To investigate the role of PC in mesothelial malignancy in the context of two-dimensional (2D) and three-dimensional (3D) phenotypes.

MATERIALS AND METHODS

The effect of pharmacological deciliation [using ammonium sulphate (AS) or chloral hydrate (CH)] and PC elongation [using lithium chloride (LC)] on cell viability, adhesion, and migration (2D cultures) as well as in mesothelial sphere formation, spheroid invasion and collagen gel contraction (3D cultures) was investigated in benign mesothelial MeT-5A cells and in malignant pleural mesothelioma (MPM) cell lines, M14K (epithelioid) and MSTO (biphasic), and primary malignant pleural mesothelioma cells (pMPM).

RESULTS

Pharmacological deciliation or elongation of the PC significantly affected cell viability, adhesion, migration, spheroid formation, spheroid invasion and collagen gel contraction in MeT-5A, M14K, MSTO cell lines and in pMPM cells compared to controls (no drug treatment).

CONCLUSIONS

Our findings indicate a pivotal role of the PC in functional phenotypes of benign mesothelial cells and MPM cells.

摘要

引言

初级纤毛(PC)是一种单一的非运动性天线状细胞器,由源自中心体母中心粒的微管核心轴突组成。初级纤毛在所有哺乳动物细胞中普遍存在,并突出到细胞外环境中,接收其在细胞内传递的机械化学信号。

目的

在二维(2D)和三维(3D)表型背景下研究初级纤毛在间皮恶性肿瘤中的作用。

材料与方法

在良性间皮MeT-5A细胞、恶性胸膜间皮瘤(MPM)细胞系M14K(上皮样)和MSTO(双相)以及原发性恶性胸膜间皮瘤细胞(pMPM)中,研究了药物去纤毛作用[使用硫酸铵(AS)或水合氯醛(CH)]和初级纤毛延长[使用氯化锂(LC)]对细胞活力、黏附、迁移(2D培养)以及间皮球形成、球体侵袭和胶原凝胶收缩(3D培养)的影响。

结果

与对照组(未进行药物处理)相比,药物去纤毛作用或初级纤毛延长显著影响了MeT-5A、M14K、MSTO细胞系和pMPM细胞的细胞活力、黏附、迁移、球体形成、球体侵袭和胶原凝胶收缩。

结论

我们的研究结果表明初级纤毛在良性间皮细胞和MPM细胞的功能表型中起关键作用。

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