TY - JOUR
T1 - Long-Pentraxin 3 Derivative as a Small-Molecule FGF Trap for Cancer Therapy
AU - Ronca, Roberto
AU - Giacomini, Arianna
AU - Di Salle, Emanuela
AU - Coltrini, Daniela
AU - Pagano, Katiuscia
AU - Ragona, Laura
AU - Matarazzo, Sara
AU - Rezzola, Sara
AU - Maiolo, Daniele
AU - Torrella, Rubben
AU - Moroni, Elisabetta
AU - Mazzieri, Roberta
AU - Escobar, Giulia
AU - Mor, Marco
AU - Colombo, Giorgio
AU - Presta, Marco
PY - 2015/8/10
Y1 - 2015/8/10
N2 - 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. Ronca et al. show that overexpression of long-pentraxin 3 (PTX3) in mice inhibits the growth of FGF-dependent tumor models. On the basis of pharmacophore modeling of PTX3-FGF2 interaction, they identify a small molecule that acts as an extracellular FGF trap and inhibits FGF-dependent tumor growth in mice.
AB - 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. Ronca et al. show that overexpression of long-pentraxin 3 (PTX3) in mice inhibits the growth of FGF-dependent tumor models. On the basis of pharmacophore modeling of PTX3-FGF2 interaction, they identify a small molecule that acts as an extracellular FGF trap and inhibits FGF-dependent tumor growth in mice.
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U2 - 10.1016/j.ccell.2015.07.002
DO - 10.1016/j.ccell.2015.07.002
M3 - Article
C2 - 26267536
AN - SCOPUS:84939444543
VL - 28
SP - 225
EP - 239
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 2
ER -