The modulation of lung cancer cell motility by Calponin 3 is achieved through its ability to sense and respond to changes in substrate stiffness

IF 3.5 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Biotechnology and Bioengineering Pub Date : 2024-09-15 DOI:10.1002/bit.28847
Yinxiu Chi, Xianhui Wang, Xiaoyun Shao, Dongliang Zhang, Jingjing Han, Linhong Deng, Liucai Yang, Xuebin Qu
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Abstract

The influence of extracellular matrix (ECM) stiffness on cell behavior is a well-established phenomenon. Tumor development is associated with the stiffening of the ECM. However, the understanding of the role of biomechanical behavior and mechanotransduction pathways in the oncogenesis of tumor cells remains limited. In this study, we constructed in vitro models using Polydimethylsiloxane substrates to create soft and stiff substrates. We then evaluated the migration of lung cancer cells A549 using video-microscopy and transwell assays. The mechanical properties were assessed through the utilization of atomic force microscopy, Optical Magnetic Twisting Cytometry, and traction force analysis. Additionally, the expression of Calponin 3 (CNN3) was evaluated using reverse transcription‑quantitative PCR and immunofluorescence techniques. Our observations indicate that the presence of a stiff substrate enhances A549 motility, as evidenced by increased stiffness and traction force in A549 cells on the stiff substrate. Furthermore, we observed a decrease in CNN3 expression in A549 cells on the stiff substrate. Notably, when CNN3 was overexpressed, it effectively inhibited the migration and invasion of A549 cells on the stiff substrate. The results of our study provide novel perspectives on the mechanisms underlying cancer cell migration in response to substrate mechanical properties.

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钙调蛋白 3 通过感知底物硬度变化并做出反应的能力来调节肺癌细胞的运动能力
细胞外基质(ECM)硬度对细胞行为的影响是一种公认的现象。肿瘤的发展与 ECM 的僵化有关。然而,人们对生物力学行为和机械传导途径在肿瘤细胞癌变过程中的作用的了解仍然有限。在本研究中,我们使用聚二甲基硅氧烷基底构建了体外模型,以创建软基底和硬基底。然后,我们使用视频显微镜和透孔试验评估了肺癌细胞 A549 的迁移情况。我们还利用原子力显微镜、光学磁扭转细胞仪和牵引力分析评估了基底的机械性能。此外,还利用逆转录定量 PCR 和免疫荧光技术评估了钙蛋白 3(CNN3)的表达。我们的观察结果表明,坚硬基底的存在增强了 A549 的运动能力,坚硬基底上 A549 细胞的硬度和牵引力增加就是证明。此外,我们还观察到僵硬基底上的 A549 细胞中 CNN3 的表达减少。值得注意的是,当 CNN3 过表达时,它能有效抑制 A549 细胞在僵硬基底上的迁移和侵袭。我们的研究结果为研究癌细胞迁移对基底机械特性的响应机制提供了新的视角。
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来源期刊
Biotechnology and Bioengineering
Biotechnology and Bioengineering 工程技术-生物工程与应用微生物
CiteScore
7.90
自引率
5.30%
发文量
280
审稿时长
2.1 months
期刊介绍: Biotechnology & Bioengineering publishes Perspectives, Articles, Reviews, Mini-Reviews, and Communications to the Editor that embrace all aspects of biotechnology. These include: -Enzyme systems and their applications, including enzyme reactors, purification, and applied aspects of protein engineering -Animal-cell biotechnology, including media development -Applied aspects of cellular physiology, metabolism, and energetics -Biocatalysis and applied enzymology, including enzyme reactors, protein engineering, and nanobiotechnology -Biothermodynamics -Biofuels, including biomass and renewable resource engineering -Biomaterials, including delivery systems and materials for tissue engineering -Bioprocess engineering, including kinetics and modeling of biological systems, transport phenomena in bioreactors, bioreactor design, monitoring, and control -Biosensors and instrumentation -Computational and systems biology, including bioinformatics and genomic/proteomic studies -Environmental biotechnology, including biofilms, algal systems, and bioremediation -Metabolic and cellular engineering -Plant-cell biotechnology -Spectroscopic and other analytical techniques for biotechnological applications -Synthetic biology -Tissue engineering, stem-cell bioengineering, regenerative medicine, gene therapy and delivery systems The editors will consider papers for publication based on novelty, their immediate or future impact on biotechnological processes, and their contribution to the advancement of biochemical engineering science. Submission of papers dealing with routine aspects of bioprocessing, description of established equipment, and routine applications of established methodologies (e.g., control strategies, modeling, experimental methods) is discouraged. Theoretical papers will be judged based on the novelty of the approach and their potential impact, or on their novel capability to predict and elucidate experimental observations.
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