Contribution of matrix metalloproteinases to hallmarks of cancer

Erik Maquoi, Benoit Detry, Charlotte Erpicum, Jenny Paupert, Silvia Blacher, Catherine Maillard and Agnès Noel

The interactions between cancer cells and their microenvironment represent a major event of tumor progression. Many carcinomas and predominately breast cancers are characterized by the formation of a reactive stroma associated with extensive type I collagen and fibrin deposition. By enmeshing cells in a dense fibrillar network, type I collagen acts as a physical barrier for cell migration. To develop metastatic capabilities, invading tumor cells must acquire the capacity to negotiate this remodeled microenvironment. In addition, infiltrating endothelial cells are also confronted to collagen barrier. How cancer cells and endothelial cells deal with interstitial collagen is not only decisive for cell migration, but also for cell survival and morphogenesis. We will discuss the mechanisms used by tumor cells to evade collagen-induced apoptosis and by lymphatic endothelial cells to deal with collagen barrier to form new lymphatics. Our recent findings are shedding light on the key contribution of interstitial collagenases during cancer progression and lymphangiogenesis.