LAUSR

Bladder tumors are a diffuse type of cancer with a relatively benign prognosis when treated at early stage/low-grade stages, but with poor outcome in the muscle invasive (MIBC) form or at recurrence. Long Pentraxin-3 (PTX3) is a component of the innate immunity with pleiotropic functions in the regulation of immune response, tissue remodeling and cancer progression. PTX3 may act as an oncosuppressor in different contexts, functioning as an antagonist of the FGF/FGFR system, rewiring the immune-microenvironment or acting through mechanisms not yet fully clarified. In this study, we report for the first time that PTX3 is differentially expressed in bladder cancer (BC) biopsies and tumor cell lines during the different stages of BC progression. Taking advantage of BC cell lines representative of different tumor grades, we demonstrate that PTX3 production by tumor cells decreases along the progression from low-grade to high grade/MIBC because of promoter methylation. In vitro and in vivo data reveal that PTX3 modulation in BC cells has a significant impact on different biological features of BC growth, including cell proliferation, motility, metabolism, stemness and drug resistance. In conclusion, PTX3 exerts an oncosuppressive effect on BC progression and may represent a potential functional biomarker in BC evolution. Citation Format: Sara Matarazzo, Laura Melocchi, Sara Rezzola, Elisabetta Grillo, Federica Maccarinelli, Arianna Giacomini, Sara Taranto, Luca Zammataro, Marianna Cerasuolo, Mattia Bugatti, William Vermi, Marco Presta, Roberto Ronca. Long Pentraxin-3 modulates bladder cancer progression [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr C121. doi:10.1158/1535-7163.TARG-19-C121