In tumors, invasive cancer cells induce matrix metalloproteinase 11 (MMP-11) expression in adjacent adipocytes (cancer-associated adipocytes), leading to their « dedifferentiation » into fibroblast-like cells. Indeed, MMP-11 is a negative regulator of adipogenesis. During my PhD, I have investigated MMP-11 function during postnatal mammary gland development. The ductal tree and alveolar structures, and milk production are reduced in MMP-11-deficient mice. Moreover, MMP-11 plays a role in collagen homeostasis. Transplantation experiments show that MMP-11 exerts an essential local paracrine function for ductal morphogenesis. Using primary mammary organoids, I show that adipocyte-related MMP-11 is a pro-branching factor in vitro. Thus, MMP-11 is a master paracrine factor during mammary gland development. Finally, to further investigate the adipocyte-related MMP-11 function, I have developed conditional transgenic mice targeting MMP-11 expression specifically into adipocytes.
