Physical confinement and distance of migration cooperatively enhance chemotherapeutic resistance in migratory GBM cells.

IF 1.6 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Physical biology Pub Date : 2025-09-30 DOI:10.1088/1478-3975/ae0dd7

Qionghua Shen, Adam Germain, Calvin Kong, Young-Tae Kim

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引用次数: 0

Abstract

Metastatic glioblastoma multiforme (GBM) is known for its dismal prognosis due to the dissemination of single cells throughout the brain parenchyma and along white matter tracts, resulting in heightened resistance to therapies. Understanding the intricate relationship between cell migration, physical confinement, and chemotherapeutic resistance in GBM is imperative for advancing treatment strategies. In this study, we employed G55, a representative migratory GBM cell line, to investigate this phenomenon. We generated three distinct cell populations: 1) cells migrating without confinement, assessed via the Scratch assay; 2) cells migrating short distance (10 μm) under confinement, examined through the Transwell assay; and 3) cells migrating long distances (> 100 μm) under confinement,studied usingthe Microchannel assay. Comparative analyses of protein expression profiles and chemotherapy sensitivity among these groups revealed that migration combined with physical confinement plays a pivotal role in augmenting chemotherapeutic resistance in interstitial invasive cancer cells. Moreover, we demonstrate the utility of the microchannel device, which facilitates controlled cell migration under physical confinement, as an effective in vitro tool for investigating metastatic cancer and associated treatment resistance. This study sheds light on the mechanisms underlying GBM progression and highlights potential avenues for therapeutic intervention. .

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物理限制和迁移距离共同增强了迁移性GBM细胞的化疗耐药性。

多形性转移性胶质母细胞瘤（GBM）因单细胞散布于整个脑实质和沿白质束而预后不佳，导致对治疗的抵抗力增强。了解细胞迁移、物理限制和GBM化疗耐药之间的复杂关系对于推进治疗策略至关重要。在本研究中，我们使用具有代表性的GBM迁移性细胞系G55来研究这一现象。我们产生了三种不同的细胞群：1)细胞在没有限制的情况下迁移，通过Scratch实验进行评估；2)细胞在封闭条件下短距离迁移（10 μm），通过Transwell实验检测；3)利用微通道实验研究了细胞在约束下长距离迁移（bbb100 μm）。这些组的蛋白表达谱和化疗敏感性的比较分析表明，迁移结合物理限制在增加间质浸润性癌细胞的化疗耐药中起关键作用。此外，我们证明了微通道装置的实用性，它有助于在物理限制下控制细胞迁移，作为研究转移性癌症和相关治疗耐药性的有效体外工具。这项研究揭示了GBM进展的潜在机制，并强调了治疗干预的潜在途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Physical biology 生物-生物物理

CiteScore

4.20

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： Physical Biology publishes articles in the broad interdisciplinary field bridging biology with the physical sciences and engineering. This journal focuses on research in which quantitative approaches – experimental, theoretical and modeling – lead to new insights into biological systems at all scales of space and time, and all levels of organizational complexity. Physical Biology accepts contributions from a wide range of biological sub-fields, including topics such as: molecular biophysics, including single molecule studies, protein-protein and protein-DNA interactions subcellular structures, organelle dynamics, membranes, protein assemblies, chromosome structure intracellular processes, e.g. cytoskeleton dynamics, cellular transport, cell division systems biology, e.g. signaling, gene regulation and metabolic networks cells and their microenvironment, e.g. cell mechanics and motility, chemotaxis, extracellular matrix, biofilms cell-material interactions, e.g. biointerfaces, electrical stimulation and sensing, endocytosis cell-cell interactions, cell aggregates, organoids, tissues and organs developmental dynamics, including pattern formation and morphogenesis physical and evolutionary aspects of disease, e.g. cancer progression, amyloid formation neuronal systems, including information processing by networks, memory and learning population dynamics, ecology, and evolution collective action and emergence of collective phenomena.