Laminin and b1 Integrins Are Crucial for Normal Mammary Gland Development in the Mouse

Here, the authors examine the role of integrin-extracellular matrix interactions in the morphogenesis of ductal structures in vivo (mouse). End buds are surrounded by a basement membrane, which is shown to contain laminin-111 and collagen IV. Blocking B1 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. Similar results were obtained with anti-laminin antibodies. In contrast, no effect on morphogenesis in vivo was seen with anti-a6 integrin antibody, suggesting that a6 is not the important partner for b1 in this system. They also show that integrins and hepatocyte growth factor (HGF) cooperate to regulate ductal morphogenesis. We propose that both laminin and b1 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.