Mammary Gland ECM Remodeling, Stiffness, and Mechanosignaling in Normal Development and Tumor Progression
Mammary Gland ECM Remodeling, Stiffness, and Mechanosignaling in Normal Development and Tumor Progression
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DOI：
10.1101/cshperspect.a003228
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发表时间：
2011-01-01
影响因子：
7.2
通讯作者：
Keely, Patricia J.
中科院分区：
文献类型：
--
作者：
Schedin, Pepper;Keely, Patricia J.
乳腺细胞与其他细胞和细胞外基质（ECM）密切接触，这两者不仅提供了生物化学背景，而且还提供了机械背景。细胞介导的收缩使细胞能够感知其微环境的硬度，并以调节基因表达和分化的适当机械信号事件作出反应。ECM的组成和组织在乳腺的整个发育过程中受到严格的调节，导致机械环境和适当的组织结构的相应调节。机械调节在乳腺癌进展过程中也起作用，因为ECM沉积、组成和组织的变化伴随着乳腺癌。这些变化导致基质变硬，激活机械信号通路，从而诱导细胞增殖，促进局部肿瘤细胞侵袭，并促进进展。因此，了解力在乳腺中的作用对于了解正常发育和病理过程至关重要。
Cells of the mammary gland are in intimate contact with other cells and with the extracellular matrix (ECM), both of which provide not only a biochemical context, but a mechanical context as well. Cell-mediated contraction allows cells to sense the stiffness of their micro-environment, and respond with appropriate mechanosignaling events that regulate gene expression and differentiation. ECM composition and organization are tightly regulated throughout development of the mammary gland, resulting in corresponding regulation of the mechanical environment and proper tissue architecture. Mechanical regulation is also at play during breast carcinoma progression, as changes in ECM deposition, composition, and organization accompany breast carcinoma. These changes result in stiffer matrices that activate mechanosignaling pathways and thereby induce cell proliferation, facilitate local tumor cell invasion, and promote progression. Thus, understanding the role of forces in the mammary gland is crucial to understanding both normal developmental and pathological processes.