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A modular microfluidic platform to study how fluid shear stress alters estrogen receptor phenotype in ER+breast cancer cells

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Microsystems & Nanoengineering 2024年第1期10卷 287-299页

作者： Braulio Andrés Ortega Quesada Jonathan Cuccia rachael coates Blake Nassar Ethan Littlefield Elizabeth C.Martin Adam T.Melvin Cain Department of Chemical Engineering Louisiana State UniversityBaton RougeLA 70803USA Department of Chemical and Biological Engineering Clemson UniversityClemsonSC 29634USA Biological and Agricultural Engineering Louisiana State UniversityBaton RougeLA 70803USA Department Medicine Section Hematology and Medical OncologyTulane UniversityNew OrleansLA 70118USA

Metastatic breast cancer leads to poor prognoses and worse outcomes in patients due to its invasive behavior and poor response to *** 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 study a modular microfluidic platform capable of mimicking the magnitude of fluid shear stress(FSS)found in human vasculature was designed and *** 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 *** of the effects of FSS on MCF-7 cells was carried out utilizing two approaches:single cell analysis and bulk *** 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 *** 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/*** demonstrated that after shearing the cells phosphorylation of p-AKT,p-mTOR,and p-STAT3 were ***,there was no change in p-ERK1/*** is a mediator of ER rapid signaling,analysis of phosphorylated ERαwas carried out and no significant differences between sheared and non-sheared populations were *** together these results demonstrate that FSS can increase phosphorylation of proteins associated with a more aggressive phenotype in circulating cancer *** findin

关键词： fluid breast estrogen

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