Matriptase/epithin participates in mammary epithelial cell growth and morphogenesis through HGF activation.
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.
Lee
Sheau-Ling
SL
Institute of Cellular and Systems Medicine, National Health Research Institutes, Taiwan, ROC. sllee@nhri.org.tw
Huang
Pao-Yi
PY
Roller
Peter
P
Cho
Eun-Gyung
EG
Park
Dongeun
D
Dickson
Robert B
RB
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D018507:Gene Expression Regulation, Developmental; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods; D010456:Peptides, Cyclic / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors
D010456:Peptides, Cyclic; D034741:RNA, Small Interfering; C448501:SFTI-1 peptide, sunflower; D017228:Hepatocyte Growth Factor; D012697:Serine Endopeptidases; C485595:matriptase