HIV protease inhibitors are potent anti-angiogenic molecules and promote regression of Kaposi sarcoma

Cecilia Sgadari; Giovanni Barillari; Elena Toschi; Davide Carlei; Ilaria Bacigalupo; Sara Baccarini; Clelia Palladino; Patrizia Leone; Roberto Bugarini; Laura Malavasi; Aurelio Cafaro; Mario Falchi; Donatella Valdembri; Giovanni Rezza; Federico Bussolino; Paolo Monini; Barbara Ensoli

doi:10.1038/nm0302-225

HIV protease inhibitors are potent anti-angiogenic molecules and promote regression of Kaposi sarcoma

Cecilia Sgadari, Giovanni Barillari, Elena Toschi, Davide Carlei, Ilaria Bacigalupo, Sara Baccarini, Clelia Palladino, Patrizia Leone, Roberto Bugarini, Laura Malavasi, Aurelio Cafaro, Mario Falchi, Donatella Valdembri, Giovanni Rezza, Federico Bussolino, Paolo Monini, Barbara Ensoli

Istituto Oncologico Candiolo

Research output: Contribution to journal › Article › peer-review

Abstract

Treatment with HIV-1 protease inhibitors (PI) is associated with a reduced incidence or regression of Kaposi sarcoma (KS). Here we show that systemic administration of the Pls indinavir or saquinavir to nude mice blocks the development and induces regression of angioproliferative KS-like lesions promoted by primary human KS cells, basic fibroblast growth factor (bFGF), or bFGF and vascular endothelial growth factor (VEGF) combined. These Pls also block bFGF or VEGF-induced angiogenesis in the chorioallantoic membrane assay with a potency similar to paclitaxel (Taxol). These effects are mediated by the inhibition of endothelial- and KS-cell invasion and of matrix metalloproteinase-2 proteolytic activation by Pls at concentrations present in plasma of treated individuals. As Pls also inhibit the in vivo growth and invasion of an angiogenic tumor-cell line, these data indicate that Pls are potent anti-angiogenic and anti-tumor molecules that might be used in treating non-HIV KS and in other HIV-associated tumors.

Original language	English
Pages (from-to)	225-232
Number of pages	8
Journal	Nature Medicine
Volume	8
Issue number	3
DOIs	https://doi.org/10.1038/nm0302-225
Publication status	Published - 2002

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Medicine(all)

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10.1038/nm0302-225

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Sgadari, C., Barillari, G., Toschi, E., Carlei, D., Bacigalupo, I., Baccarini, S., Palladino, C., Leone, P., Bugarini, R., Malavasi, L., Cafaro, A., Falchi, M., Valdembri, D., Rezza, G., Bussolino, F., Monini, P., & Ensoli, B. (2002). HIV protease inhibitors are potent anti-angiogenic molecules and promote regression of Kaposi sarcoma. Nature Medicine, 8(3), 225-232. https://doi.org/10.1038/nm0302-225

Sgadari, C, Barillari, G, Toschi, E, Carlei, D, Bacigalupo, I, Baccarini, S, Palladino, C, Leone, P, Bugarini, R, Malavasi, L, Cafaro, A, Falchi, M, Valdembri, D, Rezza, G, Bussolino, F, Monini, P & Ensoli, B 2002, 'HIV protease inhibitors are potent anti-angiogenic molecules and promote regression of Kaposi sarcoma', Nature Medicine, vol. 8, no. 3, pp. 225-232. https://doi.org/10.1038/nm0302-225

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abstract = "Treatment with HIV-1 protease inhibitors (PI) is associated with a reduced incidence or regression of Kaposi sarcoma (KS). Here we show that systemic administration of the Pls indinavir or saquinavir to nude mice blocks the development and induces regression of angioproliferative KS-like lesions promoted by primary human KS cells, basic fibroblast growth factor (bFGF), or bFGF and vascular endothelial growth factor (VEGF) combined. These Pls also block bFGF or VEGF-induced angiogenesis in the chorioallantoic membrane assay with a potency similar to paclitaxel (Taxol). These effects are mediated by the inhibition of endothelial- and KS-cell invasion and of matrix metalloproteinase-2 proteolytic activation by Pls at concentrations present in plasma of treated individuals. As Pls also inhibit the in vivo growth and invasion of an angiogenic tumor-cell line, these data indicate that Pls are potent anti-angiogenic and anti-tumor molecules that might be used in treating non-HIV KS and in other HIV-associated tumors.",

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AU - Baccarini, Sara

AU - Palladino, Clelia

AU - Leone, Patrizia

AU - Bugarini, Roberto

AU - Malavasi, Laura

AU - Cafaro, Aurelio

AU - Falchi, Mario

AU - Valdembri, Donatella

AU - Rezza, Giovanni

AU - Bussolino, Federico

AU - Monini, Paolo

AU - Ensoli, Barbara

PY - 2002

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HIV protease inhibitors are potent anti-angiogenic molecules and promote regression of Kaposi sarcoma

Abstract

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