PDF(Pubmed)
Abstract：
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 (PR and SDF1) 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.
摘要：
转移扩散后,许多激素受体阳性(HR+)患者发展为更具侵袭性的表型,观察到HRs雌激素受体(ER)和孕激素受体(PR)的缺失.在转移过程中，乳腺癌细胞暴露于高量级的流体剪切应力(FSS)。不幸的是,FSS在转移过程中调节HR表达和功能的作用尚不完全清楚。本研究旨在阐明FSS对HR+乳腺癌的影响。利用能够将乳腺癌细胞暴露于模拟原位条件的FSS的微流体平台，我们通过蛋白质和基因表达分析证明了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，由于FSS暴露和感兴趣的途径包括早期和晚期雌激素反应，540总蛋白和1473磷酸蛋白发生了显着变化。接下来评估了FSS对17β-雌二醇（E2）反应的影响，基因表达分析揭示了暴露于FSS后ER和E2介导的基因（PR和SDF1）的抑制。Western印迹显示暴露于FSS后mTOR的磷酸化增强。一起来看,这些研究为FSS对转移性乳腺癌HR信号传导的影响提供了初步见解.
