FCCC LOGO Faculty Publications
Horiguchi A , Chen DYT , Goodman OB , Zheng R , Shen R , Guan H , Hersh LB , Nanus DM
Neutral endopeptidase inhibits prostate cancer tumorigenesis by reducing FGF-2-mediated angiogenesis
Prostate Cancer and Prostatic Diseases. 2008 Mar;11(1) :79-87
PMID: ISI:000253118200012   
Back to previous list
Neutral endopeptidase ( NEP) is a cell surface peptidase that catalytically inactivates a variety of physiologically active peptides including basic fibroblast growth factor ( FGF-2). We investigated the effect of using lentivirus to overexpress NEP in NEP-deficient DU145 prostate cancer cells. Third-generation lentiviral vectors encoding wild-type NEP ( L-NEP), catalytically inactive mutant NEP ( L-NEPmu), and green fluorescent protein ( L-GFP) were stably introduced into DU145 cells. FGF-2 levels in cell culture supernatants decreased by 80% in L-NEP-infected DU145 cells compared to cells infected with L-NEPmu or L-GFP ( P<0.05) while levels of other angiogenic factors were not altered. In vitro tubulogenesis of human vascular endothelial cells induced by conditioned media from DU145 cells infected with L- NEP was significantly reduced compared with that from DU145 cells infected with L-GFP ( P<0.05). Tumor xenografts from L-NEP-infected DU145 cells were significantly smaller compared to control cell xenografts and vascularity within these tumors was decreased ( P<0.05). Our data suggest that stable expression of NEP in DU145 cells inhibits prostate cancer tumorigenicity by inhibiting angiogenesis, with a probable mechanism being proteolytic inactivation of FGF-2.
ISI Document Delivery No.: 261ZJ Times Cited: 0 Cited Reference Count: 40 Cited References: AOYAGI Y, 2004, BRIT J CANCER, V91, P1316 BASTIDE C, 2003, PROSTATE CANCER P D, V6, P228 BOGENRIEDER T, 1997, PROSTATE, V33, P225 CASSINELLI G, 2002, CLIN CANCER RES, V8, P2647 COLEMAN JE, 2003, PHYSIOL GENOMICS, V12, P221 DAI J, 2001, CLIN CANCER RES, V7, P1370 DAWSON LA, 2004, BRIT J CANCER, V90, P1577 GIAVAZZI R, 2003, AM J PATHOL, V162, P1913 GOETZE S, 2002, HYPERTENSION, V40, P748 GOODMAN OB, 2006, J BIOL CHEM, V281, P33597 GU W, 2006, CANCER GENE THER, V13, P1023 HORIGUCHI A, 2004, CLIN CANCER RES, V10, P8648 JIANG GF, 2006, CANCER BIOL THER, V5, P435 LIU AY, 2004, AM J PATHOL, V165, P1543 MACRAE EJ, 2006, PROSTATE, V66, P470 MARR RA, 2003, J NEUROSCI, V23, P1992 MORIZONO K, 2005, NAT MED, V11, P346 NAKAMOTO T, 1992, CANCER RES, V52, P571 NICHOLSON B, 2004, J CELL BIOCHEM, V91, P125 OSMAN I, 2004, CLIN CANCER RES 1, V10, P4096 OSMAN I, 2006, CANCER, V107, P2628 PAPANDREOU CN, 1998, NAT MED, V4, P50 PELLINEN R, 2004, INT J ONCOL, V25, P1753 POLNASZEK N, 2003, CANCER RES, V63, P5754 SCHOLZEN TE, 2004, EXP DERMATOL S4, V13, P22 SHEN RQ, 2000, ENDOCRINOLOGY, V141, P1699 SHIPP MA, 1991, P NATL ACAD SCI USA, V88, P10662 SMITH JA, 2001, BIOCHEM PHARMACOL, V62, P469 SUMIMOTO H, 2004, ONCOGENE, V23, P6031 SUMITOMO M, 2000, J CLIN INVEST, V106, P1399 SUMITOMO M, 2001, CANCER RES, V61, P3294 SUMITOMO M, 2004, CANCER CELL, V5, P67 TURNER AJ, 2001, BIOESSAYS, V23, P261 TURNER AJ, 2003, BIOCHEM SOC T 3, V31, P723 USMANI BA, 2000, CLIN CANCER RES, V6, P1664 VANBOKHOVEN A, 2001, CANCER RES, V61, P6340 WESLEY UV, 2005, CANCER RES, V65, P1325 YU D, 2001, CANCER GENE THER, V8, P628 YU D, 2004, PROSTATE, V59, P370 ZHENG JY, 2003, CANCER GENE THER, V10, P764 Horiguchi, A. Chen, D. Y. T. Goodman, O. B., Jr. Zheng, R. Shen, R. Guan, H. Hersh, L. B. Nanus, D. M. NATURE PUBLISHING GROUP; MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND