Laminin and β1 integrins are crucial for normal mammary gland development in the mouse
Laminin and β1 integrins are crucial for normal mammary gland development in the mouse
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DOI：
10.1006/dbio.1999.9435
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发表时间：
1999-11-01
影响因子：
2.7
通讯作者：
Streuli, CH
中科院分区：
文献类型：
--
作者：
Klinowska, TCM;Soriano, JV;Streuli, CH
我们已经研究了整合素细胞外基质相互作用的作用，在体内的导管结构的形态发生，使用发育中的小鼠乳腺作为模型。在青春期，导管从末端芽生长，形成树状网络，最终充满腺体，于是芽缩小，有丝分裂不活跃。顶芽被基底膜包围，我们发现基底膜含有层粘连蛋白-l和胶原蛋白IV。为了阐明细胞-基质相互作用在腺体发育中的作用，在青春期将分别含有功能干扰性抗β 1整联蛋白、抗α 6整联蛋白和抗层粘连蛋白抗体的颗粒植入乳腺。与对照组相比，阻断β 1整合素显著减少了每个腺体的末端芽的数量和乳腺导管网络的范围。这些效应对终芽是特异性的，因为腺体结构的其余部分保持完整。6天后发育减少仍然明显，但终芽随后重新出现，表明β 1整联蛋白的抑制是可逆的。用抗层粘连蛋白抗体获得了类似的结果。相反，抗α 6整联蛋白抗体对体内形态发生没有影响，表明ab不是该系统中β 1的重要伴侣。在导管形态发生的培养模型中证实了β 1整合素的研究，在该模型中，我们表明肝细胞生长因子（HGF）诱导的小管形成依赖于功能性β 1整合素。因此，整合素和HGF协同调节导管形态发生。我们提出，层粘连蛋白和β 1整联蛋白都是允许细胞牵引通过基质基质所必需的，因此对于维持正常青春期乳腺发育中的端芽结构和功能是必不可少的，（C）1999学术出版社。
We have examined the role of integrin-extracellular matrix interactions in the morphogenesis of ductal structures in vivo using the developing mouse mammary gland as a model. At puberty, ductal growth from terminal end buds results in an arborescent network that eventually fills the gland, whereupon the buds shrink in size and become mitotically inactive. End buds are surrounded by a basement membrane, which we show contains laminin-l and collagen IV. To address the role of cell-matrix interactions in gland development, pellets containing function-perturbing anti-beta 1 integrin, anti-alpha 6 integrin, and anti-laminin antibodies respectively were implanted into mammary glands at puberty. Blocking beta 1 integrins dramatically reduced both the number of end buds per gland and the extent of the mammary ductal network, compared with controls. These effects were specific to the end buds since the rest of the gland architecture remained intact, Reduced development was still apparent after 6 days, but end buds subsequently reappeared, indicating that the inhibition of beta 1 integrins was reversible. Similar results were obtained with anti-laminin antibodies. In contrast, no effect on morphogenesis in vivo was seen with anti-alpha 6 integrin antibody, suggesting that ab is not the important partner for beta 1 in this system. The studies with beta 1 integrin were confirmed in a culture model of ductal morphogenesis, where we show that hepatocyte growth factor (HGF)-induced tubulogenesis is dependent on functional beta 1 integrins. Thus integrins and HGF cooperate to regulate ductal morphogenesis. We propose that both laminin and beta 1 integrins are required to permit cellular traction through the stromal matrix and are therefore essential for maintaining end bud structure and function in normal pubertal mammary gland development, (C) 1999 Academic Press.