Biological and Agricultural Engineering, Louisiana State University, Baton Rouge, LA 70803, USA.
Department of Chemical and Biological Engineering, Clemson University, Clemson, SC 29634, USA.
Int J Mol Sci. 2024 Jun 28;25(13):7119. doi: 10.3390/ijms25137119.
Following metastatic spread, many hormone receptor positive (HR) patients develop a more aggressive phenotype with an observed loss of the HRs estrogen receptor (ER) and progesterone receptor (PR). During metastasis, breast cancer cells are exposed to high magnitudes of fluid shear stress (FSS). Unfortunately, the role for FSS on the regulation of HR expression and function during metastasis is not fully understood. This study was designed to elucidate the impact of FSS on HR breast cancer. Utilizing a microfluidic platform capable of exposing breast cancer cells to FSS that mimics in situ conditions, we demonstrate the impact of FSS exposure on representative HR breast cancer cell lines through protein and gene expression analysis. Proteomics results demonstrated that 540 total proteins and 1473 phospho-proteins significantly changed due to FSS exposure and pathways of interest included early and late estrogen response. The impact of FSS on response to 17β-estradiol (E2) was next evaluated and gene expression analysis revealed repression of ER and E2-mediated genes ( and ) following exposure to FSS. Western blot demonstrated enhanced phosphorylation of mTOR following exposure to FSS. Taken together, these studies provide initial insight into the effects of FSS on HR signaling in metastatic breast cancer.
在转移扩散之后，许多激素受体阳性（HR）患者的表型变得更加侵袭性，观察到激素受体雌激素受体（ER）和孕激素受体（PR）丢失。在转移过程中，乳腺癌细胞会受到高强度的流体切应力（FSS）的影响。不幸的是，FSS 对转移过程中 HR 表达和功能的调节作用尚未完全了解。本研究旨在阐明 FSS 对 HR 乳腺癌的影响。本研究利用能够使乳腺癌细胞暴露于模拟原位条件的 FSS 的微流控平台，通过蛋白质和基因表达分析，研究了 FSS 暴露对代表性 HR 乳腺癌细胞系的影响。蛋白质组学结果表明，有 540 种总蛋白和 1473 种磷酸化蛋白因 FSS 暴露而显著改变，其中包括早期和晚期雌激素反应途径。接下来评估了 FSS 对 17β-雌二醇（E2）反应的影响，基因表达分析显示，FSS 暴露后 ER 和 E2 介导的基因（和）受到抑制。Western blot 显示，FSS 暴露后 mTOR 的磷酸化增强。综上所述，这些研究为 FSS 对转移性乳腺癌中 HR 信号的影响提供了初步的见解。
