Matriptase/epithin participates in mammary epithelial cell growth and morphogenesis through HGF activation

Mech Dev. Jan-Feb 2010;127(1-2):82-95. doi: 10.1016/j.mod.2009.10.004. Epub 2009 Oct 22.

Abstract

The epithelial-derived, type II transmembrane serine protease matriptase, the mouse homologue of which is epithin, has been shown to be involved in epidermal differentiation, hair formation, and thymus function. We show in this study that epithin/matriptase (Epi/MTP) plays a significant role in mammary epithelial cell growth and morphogenesis. Epi/MTP is expressed at low level in the mouse mammary epithelium of young animals and it accumulates at the terminal end-bud of the growing ducts. The level of Epi/MTP is elevated in the mammary glands at stages when epithelial proliferation and modeling occur. It is primarily present in the luminal epithelial cells of mouse mammary ducts and lobules. Using an ex vivo three-dimensional culture system for mammary epithelial functional assays, we show that mammary epithelial growth and morphogenesis in the presence of the latent form hepatocyte growth factor (pro-HGF) are blocked either by an inhibitor of the Epi/MTP protease activity or by siRNA knockdown of the Epi/MTP expression. These studies demonstrate that Epi/MTP participates in mammary epithelial growth and modeling through activation of pro-HGF. Our findings reveal an important pathway in normal mammary epithelial morphogenesis which may participate in breast cancer progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques / methods
  • Cell Proliferation
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Developmental*
  • Hepatocyte Growth Factor / metabolism*
  • Mammary Glands, Animal / metabolism
  • Mammary Neoplasms, Animal / metabolism
  • Mice
  • Microscopy, Confocal / methods
  • Peptides, Cyclic / metabolism
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Serine Endopeptidases / metabolism
  • Serine Endopeptidases / physiology*
  • Time Factors

Substances

  • Peptides, Cyclic
  • RNA, Small Interfering
  • SFTI-1 peptide, sunflower
  • Hepatocyte Growth Factor
  • Serine Endopeptidases
  • matriptase