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Titolo:
High level synthesis of recombinant soluble urokinase receptor (CD87) by ovarian cancer cells reduces intraperitoneal tumor growth and spread in nudemice
Autore:
Lutz, V; Reuning, U; Kruger, A; Luther, T; von Steinburg, SP; Graeff, H; Schmitt, M; Wilhelm, OG; Magdolen, V;
Indirizzi:
Univ Munich, Klinikum Rechts Isar, Dept Obstet & Gynecol, Clin Res Grp, D-81675 Munich, Germany Univ Munich Munich Germany D-81675 Clin Res Grp, D-81675 Munich, Germany Tech Univ Dresden, Dept Pathol, D-01307 Dresden, Germany Tech Univ Dresden Dresden Germany D-01307 thol, D-01307 Dresden, Germany Wilex Biotechnol GMBH, D-81675 Munich, Germany Wilex Biotechnol GMBH Munich Germany D-81675 BH, D-81675 Munich, Germany
Titolo Testata:
BIOLOGICAL CHEMISTRY
fascicolo: 5, volume: 382, anno: 2001,
pagine: 789 - 798
SICI:
1431-6730(200105)382:5<789:HLSORS>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
PLASMINOGEN-ACTIVATOR RECEPTOR; ADENOVIRUS-MEDIATED DELIVERY; AMINO-TERMINAL FRAGMENT; IN-SITU HYBRIDIZATION; INHIBITOR PAI-1; BREAST-CANCER; MUTATIONAL ANALYSIS; METASTASIS; INVASION; UPA;
Keywords:
CD87; matrix degradation; ovarian cancer; soluble uPAR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Magdolen, V Univ Munich, Klinikum Rechts Isar, Dept Obstet & Gynecol, ClinRes Grp, D-81675 Munich, Germany Univ Munich Munich Germany D-81675 , D-81675 Munich, Germany
Citazione:
V. Lutz et al., "High level synthesis of recombinant soluble urokinase receptor (CD87) by ovarian cancer cells reduces intraperitoneal tumor growth and spread in nudemice", BIOL CHEM, 382(5), 2001, pp. 789-798

Abstract

Focussing of the serine protease urokinase (uPA) to the tumor cell surfacevia interaction with its receptor (uPAR) is an important step in tumor invasion and metastasis. The human ovarian cancer cell line OV-MZ-6#8 was stably transfected with expression plasmids either encoding cell-associated uPAR (GPI-uPAR) or a soluble form of uPAR (suPAR) lacking its glycan lipid anchor. In vitro, high level synthesis of functionally active recombinant suPAR inhibited cell proliferation and led to reduced cell-associated fibrin matrix degradation, whereas fibrinolytic activity was increased in OV-MZ-6#8 cells overexpressing GPI-uPAR. Both OV-MZ-6#8-derived clones were inoculated into the peritoneum of nude mice and tested for tumor growth and spread, High level synthesis of recombinant suPAR (without altering the physiological expression levels of GPI-uPAR and uPA in these cells) resulted in a significant reduction of tumor burden (up to 86%) in the xenogeneic mouse model. In contrast, overexpression of GPI-uPAR in tumor cells did not affect tumor growth. Our results demonstrate that high levels of suPAR in the ovariancancer cell vicinity can act as a potent scavenger for uPA, thereby significantly reducing tumor cell growth and cancer progression in vivo.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 23:29:28