Abrahamsson Annelie, Capodanno Alessandra, Rzepecka Anna, Dabrosin Charlotta
Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Department of Radiology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
Oncotarget. 2017 Sep 15;8(54):92134-92142. doi: 10.18632/oncotarget.20906. eCollection 2017 Nov 3.
Women with dense breast tissue on mammography are at higher risk of developing breast cancer but the underlying mechanisms are not well understood. De-regulation of microRNAs (miRNAs) has been associated with the onset of breast cancer. miRNAs in the extracellular space participate in the regulation of the local tissue microenvironment. Here, we recruited 39 healthy postmenopausal women attending their mammography-screen that were assessed having extreme dense or entirely fatty breasts (nondense). Microdialysis was performed in breast tissue and a reference catheter was inserted in abdominal subcutaneous fat for local sampling of extracellular compounds. Three miRNAs, associated with tumor suppression, miR-193b, miR-365a, and miR-452 were significantly down-regulated in dense breast tissue compared with nondense breast tissue. In addition, miR-452 exhibited significant negative correlations with several pro-inflammatory cytokines , which was confirmed by overexpression of miR-452 in breast cancer cells. No differences were found of miR-21, -29a, -30c, 146a, -148a, -203, or -451 in breast tissue and no miRs were different in plasma. Extracellular miRNAs may be among factors that should be included in studies of novel prevention strategies for breast cancer.
乳房X光检查显示乳腺组织致密的女性患乳腺癌的风险较高，但其潜在机制尚未完全明确。微小RNA（miRNA）失调与乳腺癌的发生有关。细胞外空间中的miRNA参与局部组织微环境的调节。在此，我们招募了39名接受乳房X光筛查的健康绝经后女性，她们被评估为乳房极度致密或完全为脂肪性（非致密）。在乳腺组织中进行微透析，并在腹部皮下脂肪中插入参考导管以局部采集细胞外化合物。与非致密乳腺组织相比，与肿瘤抑制相关的三种miRNA，即miR-193b、miR-365a和miR-452在致密乳腺组织中显著下调。此外，miR-452与几种促炎细胞因子呈显著负相关，这在乳腺癌细胞中miR-452过表达时得到证实。在乳腺组织中未发现miR-21、-29a、-30c、146a、-148a、-203或-451有差异，血浆中也没有miRNA存在差异。细胞外miRNA可能是乳腺癌新型预防策略研究中应考虑的因素之一。
