Mammary Gland Reprogramming: Metalloproteinases Couple Form with Function (original) (raw)

  1. Zena Werb2
  2. 1Ontario Cancer Institute/University Health Network, University of Toronto, Toronto, Ontario, M5G 2M9, Canada
  3. 2Department of Anatomy and Program in Developmental Biology, School of Medicine, University of California at San Francisco, San Francisco, California 94143-0452
  4. Correspondence: rkhokha{at}uhnres.utoronto.ca; zena.werb{at}ucsf.edu

Abstract

The adult mammary structure provides for the rapid growth, development, and immunological protection of the live-born young of mammals through its production of milk. The dynamic remodeling of the branched epithelial structure of the mammary gland in response to physiological stimuli that allow its programmed branching morphogenesis at puberty, cyclical turnover during the reproductive cycle, differentiation into a secretory organ at parturition, postlactational involution, and ultimately, regression with age is critical for these processes. Extracellular metalloproteinases are essential for the remodeling programs that operate in the tissue microenvironment at the interface of the epithelium and the stroma, coupling form with function. Deregulated proteolytic activity drives the transition of a physiological mammary microenvironment into a tumor microenvironment, facilitating malignant transformation.