Long pentraxin-3 as an epithelial-stromal fibroblast growth factor-targeting inhibitor in prostate cancer

Roberto Ronca, Patrizia Alessi, Daniela Coltrini, Emanuela Di Salle, Arianna Giacomini, Daria Leali, Michela Corsini, Mirella Belleri, Chiara Tobia, Cecilia Garlanda, Elisa Bonomi, Regina Tardanico, William Vermi, Marco Presta

Research output: Contribution to journalArticlepeer-review


Fibroblast growth factors (FGFs) exert autocrine/paracrine functions in prostate cancer by stimulating angiogenesis and tumour growth. Here dihydrotestosterone (DHT) up-regulates FGF2 and FGF8b production in murine TRAMP-C2 prostate cancer cells, activating a FGF-dependent autocrine loop of stimulation. The soluble pattern recognition receptor long pentraxin-3 (PTX3) acts as a natural FGF antagonist that binds FGF2 and FGF8b via its N-terminal domain. We demonstrate that recombinant PTX3 protein and the PTX3-derived pentapeptide Ac-ARPCA-NH2 abolish the mitogenic response of murine TRAMP-C2 cells and human LNCaP prostate cancer cells to DHT and FGFs. Also, PTX3 hampers the angiogenic activity of DHT-activated TRAMP-C2 cells on the chick embryo chorioallantoic membrane (CAM). Accordingly, human PTX3 overexpression inhibits the mitogenic activity exerted by DHT or FGFs on hPTX3-TRAMP-C2 cell transfectants and their angiogenic activity. Also, hPTX3-TRAMP-C2 cells show a dramatic decrease of their angiogenic and tumourigenic potential when grafted in syngeneic or immunodeficient athymic male mice. A similar inhibitory effect is observed when TRAMP-C2 cells overexpress only the FGF-binding N-terminal PTX3 domain. In keeping with the anti-tumour activity of PTX3 in experimental prostate cancer, immunohistochemical analysis of prostate needle biopsies from primary prostate adenocarcinoma patients shows that parenchymal PTX3 expression, abundant in basal cells of normal glands, is lost in high-grade prostatic intraepithelial neoplasia and in invasive tumour areas. These results identify PTX3 as a potent FGF antagonist endowed with anti-angiogenic and anti-neoplastic activity in prostate cancer.

Original languageEnglish
Pages (from-to)228-238
Number of pages11
JournalJournal of Pathology
Issue number2
Publication statusPublished - Jun 2013


  • androgen
  • FGF
  • pentraxin
  • prostate cancer
  • tumour growth

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


Dive into the research topics of 'Long pentraxin-3 as an epithelial-stromal fibroblast growth factor-targeting inhibitor in prostate cancer'. Together they form a unique fingerprint.

Cite this