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Titolo:
Modulation of tumor angiogenesis by conditional expression of fibroblast growth factor-2 affects early but not established tumors
Autore:
Giavazzi, R; Giuliani, R; Coltrini, D; Bani, MR; Ferri, C; Sennino, B; Tosatti, MPM; Stoppacciaro, A; Presta, M;
Indirizzi:
Mario Negri Inst Pharmacol Res, Lab Biol & Treatment Metastasis, I-24125 Bergamo, Italy Mario Negri Inst Pharmacol Res Bergamo Italy I-24125 4125 Bergamo, Italy Univ Brescia, Sch Med, Dept Biomed Sci & Technol, Unit Gen Pathol & Immunol, I-25123 Brescia, Italy Univ Brescia Brescia Italy I-25123 hol & Immunol, I-25123 Brescia, Italy Univ Brescia, Sch Med, Dept Biomed Sci & Technol, Unit Histol, I-25123 Brescia, Italy Univ Brescia Brescia Italy I-25123 , Unit Histol, I-25123 Brescia, Italy Univ La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy Univ La Sapienza Rome Italy I-00161 pt Med & Pathol, I-00161 Rome, Italy
Titolo Testata:
CANCER RESEARCH
fascicolo: 1, volume: 61, anno: 2001,
pagine: 309 - 317
SICI:
0008-5472(20010101)61:1<309:MOTABC>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELLS IN-VIVO; ENDOTHELIAL-CELLS; FACTOR OVEREXPRESSION; BINDING-PROTEIN; GENE-EXPRESSION; CANCER-THERAPY; DNA-SYNTHESIS; BRAIN-TUMORS; BFGF; INHIBITION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
70
Recensione:
Indirizzi per estratti:
Indirizzo: Presta, M Univ Brescia, Sch Med Biomed Sci & Biotechnol, Via Valsabbina 19, I-25123 Brescia, Italy Univ Brescia Via Valsabbina 19 Brescia Italy I-25123 cia, Italy
Citazione:
R. Giavazzi et al., "Modulation of tumor angiogenesis by conditional expression of fibroblast growth factor-2 affects early but not established tumors", CANCER RES, 61(1), 2001, pp. 309-317

Abstract

Fibroblast growth factor-2 (FGF2) is a pleiotropic heparin-binding growth factor endowed with a potent angiogenic activity in vitro and in vivo. To investigate the impact of the modulation of FGF2 expression on the neovascularization at different stages of tumor growth, we generated stable transfectants (Tet-FGF2) from the human endometrial adenocarcinoma HEC-1-B cell line in which FGF2 expression is under the control of the tetracycline-responsive promoter (Tet-off system). After transfection, independent clones were obtained in which FGF2 mRNA and protein were up-regulated compared with parental cells. Also, the conditioned medium of Tet-FGF2 transfectants caused proliferation, urokinase-type plasminogen activator up-regulation, migration, and sprouting of cultured endothelial cells. A 3-day treatment of Tet-FGF2 cell cultures with tetracycline abolished FGF2 overexpression and the biological activity of the conditioned medium without affecting their proliferative capacity. Tet-FGF2 cells formed tumors when nude mice received s.c. injections. The administration of 2.0 mg/ml tetracycline in the drinking water before cell transplantation, continued throughout the whole experiment, inhibited FGF2 expression in Tet-FGF2 tumor lesions. This was paralleled by a significant decrease in the rate of tumor growth and vascularization to values similar to those observed in lesions generated by parental HEC-1-B cells. Tetracycline administration 20 days after tumor cell, implant, although equally effective in reducing FGF2 expression and inhibiting tumor vascularity, only minimally impaired the growth of established Tet-FGF2 tumors. The results indicate that FGF2 expression deeply affects the initial tumorgrowth and neovascularization of HEC-1-B human endometrial adenocarcinoma in nude mice. On the contrary, the growth of established tumors appears to be independent of the inhibition of FGF2 expression and decreased vascular density. The possibility that a significant reduction of angiogenesis may not affect the progression of large tumors points to the use of antiangiogenic therapy in early tumor stage.

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Documento generato il 30/11/20 alle ore 16:19:05