Ditto Maggie, Jacho Diego, Eisenmann Kathryn M, Yildirim-Ayan Eda
Department of Bioengineering, College of Engineering, University of Toledo, Toledo, OH 43606, USA.
Department of Cell and Cancer Biology, College of Medicine and Life Sciences, University of Toledo Health Science Campus, Toledo, OH 43614, USA.
Bioengineering (Basel). 2023 Oct 31;10(11):1271. doi: 10.3390/bioengineering10111271.
This study aimed to understand extracellular mechanical stimuli's effect on prostate cancer cells' metastatic progression within a three-dimensional (3D) bone-like microenvironment. In this study, a mechanical loading platform, EQUicycler, has been employed to create physiologically relevant static and cyclic mechanical stimuli to a prostate cancer cell (PC-3)-embedded 3D tissue matrix. Three mechanical stimuli conditions were applied: control (no loading), cyclic (1% strain at 1 Hz), and static mechanical stimuli (1% strain). The changes in prostate cancer cells' cytoskeletal reorganization, polarity (elongation index), proliferation, expression level of N-Cadherin (metastasis-associated gene), and migratory potential within the 3D collagen structures were assessed upon mechanical stimuli. The results have shown that static mechanical stimuli increased the metastasis progression factors, including cell elongation ( < 0.001), cellular F-actin accumulation ( < 0.001), actin polymerization ( < 0.001), N-Cadherin gene expression, and invasion capacity of PC-3 cells within a bone-like microenvironment compared to its cyclic and control loading counterparts. This study established a novel system for studying metastatic cancer cells within bone and enables the creation of biomimetic in vitro models for cancer research and mechanobiology.
本研究旨在了解细胞外机械刺激对前列腺癌细胞在三维(3D)类骨微环境中转移进程的影响。在本研究中,采用了一种机械加载平台EQUicycler,对嵌入前列腺癌细胞(PC-3)的3D组织基质施加生理相关的静态和循环机械刺激。施加了三种机械刺激条件:对照(无加载)、循环(1Hz下1%应变)和静态机械刺激(1%应变)。在机械刺激后,评估了前列腺癌细胞在3D胶原结构内的细胞骨架重组、极性(伸长指数)、增殖、N-钙黏蛋白(转移相关基因)表达水平和迁移潜能的变化。结果表明,与循环加载和对照加载相比,静态机械刺激增加了转移进展因子,包括细胞伸长(<0.001)、细胞F-肌动蛋白积累(<0.001)、肌动蛋白聚合(<0.001)、N-钙黏蛋白基因表达以及PC-3细胞在类骨微环境中的侵袭能力。本研究建立了一种用于研究骨内转移癌细胞的新型系统,并能够创建用于癌症研究和力学生物学的仿生体外模型。