Abstract
Bladder tumors are a diffuse type of cancer. 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 fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) system, rewiring the immune microenvironment, or acting through mechanisms not yet fully clarified. In this study we used biopsies and data mining to assess that PTX3 is differentially expressed during the different stages of bladder cancer (BC) progression. BC cell lines, representative of different tumor grades, and transgenic/carcinogen-induced models were used to demonstrate in vitro and in vivo that PTX3 production by tumor cells decreases along the progression from low-grade to high-grade advanced muscle invasive forms (MIBC). In vitro and in vivo data revealed for the first time that PTX3 modulation and the consequent impairment of FGF/FGR systems in BC cells have a significant impact on different biological features of BC growth, including cell proliferation, motility, metabolism, stemness, and drug resistance. PTX3 exerts an oncosuppressive effect on BC progression and may represent a potential functional biomarker in BC evolution. Moreover, FGF/FGFR blockade has an impact on drug resistance and stemness features in BC.
Highlights
Bladder cancer (BC) is one of the most common cancers in the world, its worldwide incidence being estimated in more than 2 million patients per year, with a death rate of 400,000/year
Are low-grade superficial papillary/non-muscle invasive tumors (NMIBC) with a relatively benign prognosis; the remaining 30% of urothelial carcinomas (UC) are diagnosed as advanced muscle invasive forms (MIBC) with generally poor outcomes [1]
We demonstrate that PTX3 production by tumor cells decreases along the progression from low-grade to high-grade/muscle invasive bladder cancer (MIBC), with an oncosuppressive impact on the biological features of bladder cancer (BC) growth, including tumor cell proliferation, motility, metabolism, stemness, and drug resistance
Summary
Bladder cancer (BC) is one of the most common cancers in the world, its worldwide incidence being estimated in more than 2 million patients per year, with a death rate of 400,000/year (source NCI, SEER Cancer Statistics Review). Are low-grade superficial papillary/non-muscle invasive tumors (NMIBC) with a relatively benign prognosis; the remaining 30% of UC are diagnosed as advanced muscle invasive forms (MIBC) with generally poor outcomes [1]. The conventional treatment of NMIBC involves surgical resection and intravesical chemo- or immunotherapy. One of the major challenges in the management of these tumors is their propensity to recur, requiring frequent and lifelong surveillance and making superficial. 15% of superficial tumors progress to become invasive. Despite treatment with radical cystectomy, radiotherapy, and adjuvant or neoadjuvant chemotherapy, newly diagnosed invasive bladder tumors
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