CD44v6 Is Associated with Tumor Aggressiveness and Chemoresistance in Bladder Cancer
Bladder cancer represents a significant clinical and public health challenge. This malignancy is characterized by a very high propensity for recurrence and progression, underscoring the critical need for novel biomarkers to enhance early detection, prognosis, and specific therapeutic strategies. In the quest for such biomarkers, the CD44 family, particularly its variant isoform CD44v6, has emerged as a molecule of interest due to its pivotal roles in tumorigenesis and cell migration. Here we present a comprehensive study that elucidates the expression patterns and functional significance of CD44 and CD44v6 in bladder cancer. Utilizing robust methodological frameworks that include gene expression analyses, immunohistochemistry for protein localization, and a series of in vitro and in vivo functional assays, we systematically investigate the roles of these glycoproteins in bladder cancer pathology. Our analysis demonstrates a strong association between either elevated CD44 or CD44v6 expression and adverse clinical outcomes. Functional investigations attribute enhanced proliferative, migratory, and invasive capacities of bladder cancer cells to CD44v6 expression, indicating its contributory role in tumor aggressiveness and, importantly, in resistance to cisplatin treatment. In summary, our study places CD44 and CD44v6 as key biomarkers and putative therapeutic targets in bladder cancer. By shedding light on their mechanistic roles in cancer progression, we pave the way for the development of targeted therapeutic strategies that could potentially improve patient management and outcomes in bladder cancer. Overall design: Analysis of bladder cancer cell lines, including J82 and RT-112 parental cell lines, as well as newly established J82 CD44 Low, J82 CD44 High, J82 CD44v6 and RT-112 CD44 Low, RT-112 CD44 High and RT-112 CD44v6 cell lines, by means of RNASeq analysis. CD44 Low cell lines represent low CD44 receptor expression, CD44 High cell lines show high CD44 receptor expression and CD44v6 cell lines present high CD44v6 receptor expression. Comparative analyses between the different cell lines were performed. 3 biological replicates of each cell line were included in this analysis.