The fibroblast growth factor (FGF)/FGF receptor (FGFR) system plays a crucial role in cancer by affecting tumor growth, angiogenesis, drug resistance, and escape from anti-angiogenic anti-vascular endothelial growth factor therapy. The soluble pattern recognition receptor long-pentraxin 3 (PTX3) acts as a multi-FGF antagonist. Here we demonstrate that human PTX3 overexpression in transgenic mice driven by the Tie2 promoter inhibits tumor growth, angiogenesis, and metastasis in heterotopic, orthotopic, and autochthonous FGF-dependent tumor models. Using pharmacophore modeling of the interaction of a minimal PTX3-derived FGF-binding pentapeptide with FGF2, we identified a small-molecule chemical (NSC12) that acts as an extracellular FGF trap with significant implications in cancer therapy.
Long-Pentraxin 3 Derivative as a Small-Molecule FGF Trap for Cancer Therapy / Ronca, R., Giacomini, A., Di Salle, E., Coltrini, D., Pagano, K., Ragona, L., Matarazzo, S., Rezzola, S., Maiolo, D., Torrella, R., Moroni, E., Mazzieri, R., Escobar, G., Mor, M., Colombo, G., Presta, M.. - In: CANCER CELL. - ISSN 1535-6108. - 28:2(2015), pp. 225-239. [10.1016/j.ccell.2015.07.002]
Long-Pentraxin 3 Derivative as a Small-Molecule FGF Trap for Cancer Therapy
MOR, Marco;
2015-01-01
Abstract
The fibroblast growth factor (FGF)/FGF receptor (FGFR) system plays a crucial role in cancer by affecting tumor growth, angiogenesis, drug resistance, and escape from anti-angiogenic anti-vascular endothelial growth factor therapy. The soluble pattern recognition receptor long-pentraxin 3 (PTX3) acts as a multi-FGF antagonist. Here we demonstrate that human PTX3 overexpression in transgenic mice driven by the Tie2 promoter inhibits tumor growth, angiogenesis, and metastasis in heterotopic, orthotopic, and autochthonous FGF-dependent tumor models. Using pharmacophore modeling of the interaction of a minimal PTX3-derived FGF-binding pentapeptide with FGF2, we identified a small-molecule chemical (NSC12) that acts as an extracellular FGF trap with significant implications in cancer therapy.| File | Dimensione | Formato | |
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