Institute of Biomedicine and Cancer Research Laboratory FICAN West, University of Turku, FI-20520 Turku, Finland; Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland.
Institute of Biomedicine and Cancer Research Laboratory FICAN West, University of Turku, FI-20520 Turku, Finland; Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland.
Semin Cell Dev Biol. 2021 Jun;114:113-125. doi: 10.1016/j.semcdb.2020.10.010. Epub 2020 Nov 10.
The mammary gland is dynamically remodelled during its postnatal development and the reproductive cycles. This inherent plasticity has been suggested to increase the susceptibility of the organ to carcinogenesis. Morphological changes in the mammary epithelium involve cell proliferation, differentiation, apoptosis, and migration which, in turn, are affected by cell adhesion to the extracellular matrix (ECM). Integrin adhesion receptors function in the sensing of the biochemical composition, patterning and mechanical properties of the ECM surrounding the cells, and strongly influence cell fate. This review aims to summarize the existing literature on how different aspects of integrin-mediated adhesion and mechanosensing, including ECM composition; stiffness and topography; integrin expression patterns; focal adhesion assembly; dynamic regulation of the actin cytoskeleton; and nuclear mechanotransduction affect mammary gland development, function and homeostasis. As the mechanical properties of a complex tissue environment are challenging to replicate in vitro, emphasis has been placed on studies conducted in vivo or using organoid models. Outright, these studies indicate that mechanosensing also contributes to the regulation of mammary gland morphogenesis in multiple ways.
乳腺在其出生后的发育和生殖周期中会进行动态重塑。这种固有可塑性被认为增加了器官发生癌变的易感性。乳腺上皮组织的形态变化涉及细胞增殖、分化、凋亡和迁移,而这些过程又受到细胞与细胞外基质(ECM)的黏附的影响。整合素黏附受体在感知细胞周围 ECM 的生化组成、模式和力学特性方面发挥作用,并强烈影响细胞命运。这篇综述旨在总结现有文献,阐述整合素介导的黏附和机械感知的各个方面,包括 ECM 组成、硬度和形貌、整合素表达模式、焦点黏附组装、肌动蛋白细胞骨架的动态调节以及核机械转导,如何影响乳腺的发育、功能和稳态。由于复杂组织环境的力学特性在体外很难复制,因此本研究强调了在体内或使用类器官模型进行的研究。这些研究表明,机械感知也通过多种方式有助于调节乳腺形态发生。