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 were poorly 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 inhibitor tissue 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 was also enhanced by heparin, implying that HIV-1 rat could contribute to the aetiology of HIV-associated KS. Conclusions: KS-like lesions were obtained by injecting cell-free secreted products, suggesting that KS is 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.
|Autori interni:||FONTANINI, GABRIELLA|
|Autori:||ALBINI A; FONTANINI G; MASIELLO L; TACCHETTI C; BIGINI D; LUZZI P; NOONAN DM; STETLERSTEVENSON WG|
|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|
|Anno del prodotto:||1994|
|Digital Object Identifier (DOI):||10.1097/00002030-199409000-00004|
|Appare nelle tipologie:||1.1 Articolo in rivista|