hPTX3 overexpression blocks tumor growth and metastases in transgenic mice
•
Pharmacophore modeling identified NSC12 as a PTX3-derived anti-FGF small molecule
•
NSC12 inhibits FGF-dependent tumor growth, angiogenesis, and metastases
•
NSC12 acts as a small-molecule FGF trap in cancer therapy
Summary
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.
