Extracellular signals in young and aging breast epithelial cells and possible connections to age-associated breast cancer development

► Extracellular signals by MMP-7 and HB-EGF are compared in young and aging HMEC. ► Growth signals are relayed via HB-EGF and 4ICD of the ErbB4 receptor in young HMEC. ► An accumulation of aging HMEC is associated with enhanced ECM formation. ► MMP-7 and sHB-EGF can contribute to fibrosis by cleavage of ECM compounds. ► Fibrosis could support EMT and growth of neoplastic cells in aging breast tissue.