Glycosylated LGALS3BP is highly secreted by bladder cancer cells and represents a novel urinary disease biomarker

: Bladder cancer incidence has recently risen, making it the ninth most diagnosed cancer, highlighting an urgent need for novel and effective diagnostic and therapeutic strategies to improve patient outcomes. Here, we report on a secreted glycoprotein, Galectin-3-binding protein (LGALS3BP), as a potential biomarker and therapeutic target for bladder cancer. We found a significantly elevated LGALS3BP expression in bladder cancer tissues, correlating with disease progression. Moreover, urinary and serum levels of LGALS3BP were significantly higher in patients compared to healthy individuals, with a strong correlation observed between elevated urinary protein levels and tumor grade. Of note, LGALS3BP produced by tumor cells treated with a mannosidase I inhibitor, Kifunensine, exhibited increased reactivity to a therapeutic antibody (denoted as "1959"), suggesting that glycosylation of LGALS3BP may influence antibody recognition and protein function. Furthermore, administration of 1959-sss/DM4 antibody-drug conjugate in two xenograft mouse models of human bladder cancer resulted in complete inhibition of tumor growth. In summary, findings presented here highlight LGALS3BP as a promising candidate for further investigation into its potential as a urinary biomarker and a therapeutic target for bladder cancer.