Hepsin promotes prostate cancer progression and metastasis.
The majority of cancer-related deaths are associated with metastasis; however, little is known about the mechanisms of this process. Hepsin is a cell surface serine protease that is markedly upregulated in human prostate cancer; however, the functional significance of this upregulation is unknown. We report here that hepsin overexpression in prostate epithelium in vivo causes disorganization of the basement membrane. Overexpression of hepsin in a mouse model of nonmetastasizing prostate cancer has no impact on cell proliferation, but causes disorganization of the basement membrane and promotes primary prostate cancer progression and metastasis to liver, lung, and bone. We provide in vivo evidence that upregulation of a cell surface serine protease in a primary tumor promotes cancer progression and metastasis.
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Olga
O
Klezovitch
John
J
Chevillet
Janni
J
Mirosevich
Richard L
RL
Roberts
Robert J
RJ
Matusik
Valeri
V
Vasioukhin
D000818:Animals; D017209:Apoptosis; D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D002454:Cell Differentiation; D002455:Cell Division; D004195:Disease Models, Animal; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D011467:Prostate / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*
D008565:Membrane Proteins; D012697:Serine Endopeptidases; C055645:hepsin