A modular microfluidic platform to study how fluid shear stress alters estrogen receptor phenotype in ER+breast cancer cells
作者机构：Cain Department of Chemical EngineeringLouisiana State UniversityBaton RougeLA 70803USA Department of Chemical and Biological EngineeringClemson UniversityClemsonSC 29634USA Biological and Agricultural EngineeringLouisiana State UniversityBaton RougeLA 70803USA Department MedicineSection Hematology and Medical OncologyTulane UniversityNew OrleansLA 70118USA
出 版 物：《Microsystems & Nanoengineering》 (微系统与纳米工程（英文）)
年 卷 期：2024年第10卷第1期
页 面：287-299页
核心收录：
学科分类：1002[医学-临床医学] 0804[工学-仪器科学与技术] 0805[工学-材料科学与工程（可授工学、理学学位）] 100214[医学-肿瘤学] 10[医学]
基 金：funded by the National Institute of Health(R03CA262944 ECM/ATM)。
摘 要：Metastatic breast cancer leads to poor prognoses and worse outcomes in patients due to its invasive behavior and poor response to therapy.It is still unclear what biophysical and biochemical factors drive this more aggressive phenotype in metastatic cancer;however recent studies have suggested that exposure to fluid shear stress in the vasculature could cause this.In this study a modular microfluidic platform capable of mimicking the magnitude of fluid shear stress(FSS)found in human vasculature was designed and fabricated.This device provides a platform to evaluate the effects of FSS on MCF-7 cell line,an estrogen receptor positive(ER+)breast cancer cell line,during circulation in the vessels.Elucidation of the effects of FSS on MCF-7 cells was carried out utilizing two approaches:single cell analysis and bulk analysis.For single cell analysis,cells were trapped in a microarray after exiting the serpentine channel and followed by immunostaining on the device(on-chip).Bulk analysis was performed after cells were collected in a microtube at the outlet of the microfluidic serpentine channel for western blotting(off-chip).It was found that cells exposed to an FSS magnitude of 10 dyn/cm^(2) with a residence time of 60 s enhanced expression of the proliferation marker Ki67 in the MCF-7 cell line at a single cell level.To understand possible mechanisms for enhanced Ki67 expression,on-chip and off-chip analyses were performed for pro-growth and survival pathways ERK,AKT,and JAK/STAT.Results demonstrated that after shearing the cells phosphorylation of p-AKT,p-mTOR,and p-STAT3 were observed.However,there was no change in p-ERK1/2.AKT is a mediator of ER rapid signaling,analysis of phosphorylated ERαwas carried out and no significant differences between sheared and non-sheared populations were observed.Taken together these results demonstrate that FSS can increase phosphorylation of proteins associated with a more aggressive phenotype in circulating cancer cells.These findings provide additional information that may help inform why cancer cells located at metastatic sites are usually more aggressive than primary breast cancer cells.
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