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Titolo:
ANGIOGENIC POTENTIAL IN-VIVO BY KAPOSIS-SARCOMA CELL-FREE SUPERNATANTS AND HIV-1 TAT PRODUCT - INHIBITION OF KS-LIKE LESIONS BY TISSUE INHIBITOR OF METALLOPROTEINASE-2
Autore:
ALBINI A; FONTANINI G; MASIELLO L; TACCHETTI C; BIGINI D; LUZZI P; NOONAN DM; STETLERSTEVENSON WG;
Indirizzi:
IST NAZL RIC CANC,DEPT CHEM CARCINOGENESIS,VIALE BENEDETTO 15,10 I-16132 GENOA ITALY UNIV PISA,INST PATHOL ANAT PISA ITALY UNIV GENOA,INST ANAT GENOA ITALY NCI BETHESDA MD 00000
Titolo Testata:
AIDS
fascicolo: 9, volume: 8, anno: 1994,
pagine: 1237 - 1244
SICI:
0269-9370(1994)8:9<1237:APIBKC>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSGENIC MICE; AIDS; GROWTH; EXPRESSION; INVITRO; CULTURE; GENE; PROLIFERATION; INVASIVENESS; TIMP-2;
Keywords:
KAPOSIS SARCOMA; HIV; FAT; ANGIOGENESIS; HEPARIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
31
Recensione:
Indirizzi per estratti:
Citazione:
A. Albini et al., "ANGIOGENIC POTENTIAL IN-VIVO BY KAPOSIS-SARCOMA CELL-FREE SUPERNATANTS AND HIV-1 TAT PRODUCT - INHIBITION OF KS-LIKE LESIONS BY TISSUE INHIBITOR OF METALLOPROTEINASE-2", AIDS, 8(9), 1994, pp. 1237-1244

Abstract

Objective: To determine the neoplastic nature of Kaposi's sarcoma (KS). A highly vascularized lesion, KS is frequently associated with AIDS, indicating HIV products may be involved. Design and methods: We determined the angiogenic properties of KS cell-secreted products and the HIV-1-tat gene product in vivo. Cell-free secreted products (KS-CM) from cultured epidemic and sporadic KS spindle cells or recombinant (r) HIV-1 tat protein were injected into mice with a matrix support (Matrigel).Results: KS-CM produced lesions carrying all the phenotypic hallmarks of KS, as observed by light and electron microscopy: spindle-shaped cells, haemorrhages and an inflammatory infiltrate, as well as Factor VIII-positive endothelial cells lining new blood vessels. Electron microscopy indicated an initial granulocyte invasion, with spindle-cell migration and neocapillary formation in the centre or the matrix. These lesions required the cofactor heparin; KS-CM or heparin alone werepoorly angiogenic. A less intense angiogenesis, with lower cellularity and few granulocytes, was observed in basic fibroblast growth factor(bFGF)/heparin lesions, indicating that factors other than bFGF are present in the KS spindle-cell products. When the collagenase inhibitortissue inhibitor of metalloproteinases (TIMP)-2 was added to the sponges, KS-CM-induced angiogenesis was reduced by approximately 65% and bFCF-induced angiogenesis inhibited completely. Recombinant HIV-1 tat protein, a growth factor for KS cells, induced vascularization that wasalso enhanced by heparin, implying that HIV-1 rat could contribute tothe aetiology of HIV-associated KS. Conclusions: KS-like lesions wereobtained by injecting cell-free secreted products, suggesting that KSis a 'self-propagating' proliferative lesion caused by a cytokine imbalance and not a true neoplasm. Heparin-binding factors appear to be involved, and HIV-1 tar angiogenic properties implicate this molecule in AIDS-associated KS. Inhibition of KS-CM-induced KS-like lesions by TIMP-2 suggests that metalloproteinase inhibitors could be potential therapeutic agents for KS.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 19:49:37