Soluble epithin/PRSS14 secreted from cancer cells contains active angiogenic potential.
Epithin (PRSS14/matriptase/ST14), a type II membrane protein, is involved in progression of epithelial cancers and metastasis as well as in the normal epidermal barrier function. When activated, it translocates into the cell-cell contacts and sheds into media. In order to understand the specific mechanism during tumor progression, we tested the angiogenic potential of secreted form of epithin. Epithin produced from the cancer cells shed more in hypoxia and induced motility of endothelial cells. Epithin enhanced the migration and invasion of mouse and bovine endothelial cells without cell proliferation. Furthermore, soluble epithin induced endothelial differentiation in the assay of the human endothelial microvessel-like tube formation and in that of the chicken chorioallantoic membrane. The knock-down of epithin in the 427 thymoma cell line abolished the protease activity of secreted epithin fraction, reduced the invasion of endothelial cells through matrigel, and tube formation activity. Only specific antibodies abolished the migration of endothelial cell and the vessel morphogenesis, suggesting that epithin specifically functions in these systems. Therefore, we propose that the secreted epithin in the hypoxic cancer microenvironment plays a role as a proangiogenic factor, and can be modulated with specific antibodies.
Kim
Sang Bum
SB
School of Biological Sciences, Seoul National University, Seoul, 151-747, Korea.
Lee
Deokjae
D
Jeong
Joo-Won
JW
Kim
Chungho
C
Park
Dongeun
D
Kim
Moon Gyo
MG
D043925:Angiogenesis Inducing Agents / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001808:Blood Vessels / Q000254:growth & development; D002277:Carcinoma / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002417:Cattle; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000254:growth & development; D018450:Disease Progression; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008546:Melanoma, Experimental; D008565:Membrane Proteins; D051379:Mice; D009024:Morphogenesis / Q000187:drug effects / Q000235:genetics; D041681:NIH 3T3 Cells; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009389:Neovascularization, Pathologic; D034741:RNA, Small Interfering / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics
D043925:Angiogenesis Inducing Agents; D000911:Antibodies, Monoclonal; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D012697:Serine Endopeptidases; C485596:ST14 protein, human; C118992:St14 protein, mouse