乳腺癌中的机械微环境

Pratt Stephen J P, Lee Rachel M, Martin Stuart S

Program in Biochemistry and Molecular Biology, Department of Physiology, and Marlene and Stewart Greenebaum NCI Cancer Center, University of Maryland School of Medicine, 655 W. Baltimore Street, Bressler Research Building, Rm 10-020 D, Baltimore, MD 21201, USA.

Department of Physiology and Marlene and Stewart Greenebaum NCI Cancer Center, University of Maryland School of Medicine, 655 W. Baltimore Street, Bressler Research Building, Rm 10-020 D, Baltimore, MD 21201, USA.

Cancers (Basel). 2020 Jun 3;12(6):1452. doi: 10.3390/cancers12061452.

Mechanotransduction is the interpretation of physical cues by cells through mechanosensation mechanisms that elegantly translate mechanical stimuli into biochemical signaling pathways. While mechanical stress and their resulting cellular responses occur in normal physiologic contexts, there are a variety of cancer-associated physical cues present in the tumor microenvironment that are pathological in breast cancer. Mechanistic in vitro data and in vivo evidence currently support three mechanical stressors as mechanical modifiers in breast cancer that will be the focus of this review: stiffness, interstitial fluid pressure, and solid stress. Increases in stiffness, interstitial fluid pressure, and solid stress are thought to promote malignant phenotypes in normal breast epithelial cells, as well as exacerbate malignant phenotypes in breast cancer cells.

机械转导是细胞通过机械感觉机制对物理信号的解读，这些机制能巧妙地将机械刺激转化为生化信号通路。虽然机械应力及其引发的细胞反应发生在正常生理环境中，但肿瘤微环境中存在多种与癌症相关的物理信号，在乳腺癌中这些信号是病理性的。目前，体外机制数据和体内证据支持三种机械应激源作为乳腺癌中的机械调节因子，它们将是本综述的重点：硬度、间质液压力和固体应力。硬度、间质液压力和固体应力的增加被认为会促进正常乳腺上皮细胞中的恶性表型，以及加剧乳腺癌细胞中的恶性表型。