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Deciphering Biophysical Modulation in Ovarian Cancer Cells
Cell Biochemistry and Biophysics ( IF 2.6 ) Pub Date : 2021-01-12 , DOI: 10.1007/s12013-020-00964-9
Makhdoom Sarwar 1 , Peter H Sykes 1 , Kenny Chitcholtan 1 , John J Evans 1, 2
Affiliation  

It has been long known that the oncogenic extracellular environment plays an indispensable role in developing and nurturing cancer cell progression and in resistance to standard treatments. However, by how much the biophysical components of tumour extracellular environment contribute to these processes is uncertain. In particular, the topographic environment is scarcely explored. The biophysical modulation of cell behaviour is primarily facilitated through mechanotransduction-associated mechanisms, including focal adhesion and Rho/ROCK signalling. Dysregulation of these pathways is commonly observed in ovarian cancer and, therefore, biophysical modulation of these mechanisms may be of great importance to ovarian cancer development and progression. In this work, aspects of the biophysical environment were explored using a bioimprinting technique. The study showed that topography-mediated substrate sensing delayed cell attachment, however, cell–cell interactions overrode the effect of topography in some cell lines, such as OVCAR-5. Also, 3D topographical cues were shown to modulate the inhibition of focal adhesion and Rho signalling, which resulted in higher MAPK activity in cells on the bioimprints. It was revealed that c-Src is vital to the biophysical modulation of cell proliferation and inhibition of c-Src could downregulate biophysically modulated MAPK activity. This study provides evidence that the biophysical extracellular environment affects key intracellular mechanisms associated with tumourigenicity in ovarian cancer cells.



中文翻译:

破译卵巢癌细胞中的生物物理调制

众所周知,致癌细胞外环境在发展和培养癌细胞进展以及对标准治疗的抵抗中起着不可或缺的作用。然而,肿瘤细胞外环境的生物物理成分对这些过程的贡献程度尚不确定。特别是,地形环境几乎没有被探索。细胞行为的生物物理调节主要通过机械转导相关机制促进,包括粘着斑和 Rho/ROCK 信号。在卵巢癌中通常观察到这些途径的失调,因此,这些机制的生物物理调节可能对卵巢癌的发展和进展非常重要。在这项工作中,使用生物印迹技术探索了生物物理环境的各个方面。该研究表明,地形介导的底物感应延迟了细胞附着,然而,细胞间相互作用在某些细胞系(如 OVCAR-5)中压倒了地形的影响。此外,显示 3D 地形线索可调节粘着斑和 Rho 信号传导的抑制,这导致生物印记上细胞中更高的 MAPK 活性。结果表明,c-Src 对细胞增殖的生物物理调节至关重要,c-Src 的抑制可以下调生物物理调节的 MAPK 活性。这项研究提供的证据表明,生物物理细胞外环境影响与卵巢癌细胞致瘤性相关的关键细胞内机制。在某些细胞系(如 OVCAR-5)中,细胞间相互作用超过了地形的影响。此外,显示 3D 地形线索可调节粘着斑和 Rho 信号传导的抑制,这导致生物印记上细胞中更高的 MAPK 活性。结果表明,c-Src 对细胞增殖的生物物理调节至关重要,c-Src 的抑制可以下调生物物理调节的 MAPK 活性。这项研究提供的证据表明,生物物理细胞外环境影响与卵巢癌细胞致瘤性相关的关键细胞内机制。在某些细胞系(如 OVCAR-5)中,细胞间相互作用超过了地形的影响。此外,显示 3D 地形线索可调节粘着斑和 Rho 信号传导的抑制,这导致生物印记上细胞中更高的 MAPK 活性。结果表明,c-Src 对细胞增殖的生物物理调节至关重要,c-Src 的抑制可以下调生物物理调节的 MAPK 活性。这项研究提供的证据表明,生物物理细胞外环境影响与卵巢癌细胞致瘤性相关的关键细胞内机制。结果表明,c-Src 对细胞增殖的生物物理调节至关重要,c-Src 的抑制可以下调生物物理调节的 MAPK 活性。这项研究提供的证据表明,生物物理细胞外环境影响与卵巢癌细胞致瘤性相关的关键细胞内机制。结果表明,c-Src 对细胞增殖的生物物理调节至关重要,c-Src 的抑制可以下调生物物理调节的 MAPK 活性。这项研究提供的证据表明,生物物理细胞外环境影响与卵巢癌细胞致瘤性相关的关键细胞内机制。

更新日期:2021-01-12
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