Cancer stem cells in bladder cancer: a revisited and evolving concept

Abstract

Recently, the prospective isolation and characterization of cancer stem cells (CSCs) from various human malignancies revealed that they are resistant to radiation and chemotherapies. Therefore, CSCs may be the 'roots' and ideal target for therapeutic intervention. Here, we will focus on reviewing the historical perspective, recent literatures on bladder cancer stem cells and their clinical implications. CSCs have been prospectively isolated from bladder cancer tissues from patient specimens, established cancer cell lines and xenografts, based on the expression of a combination of cell surface receptors, cytokeratin markers, drug transporters and the efficient efflux of the Hoechst 33,342 dye (side population). Further, global gene expression profiling of CSCs revealed an activated gene signature of CSCs similar to that of aggressive bladder cancer, supporting the concept that a tumor cell subpopulation is contributing to bladder cancer progression. Finally, our studies on the preclinical targeting of bladder CSCs in vitro and in xenografts using a blocking antibody for CD47 reveal promising efficacy. Functionally distinct CSCs exist in human bladder cancer and can be prospectively isolated. Continuing research will be important to identify their cell of origin, programs balancing self-renewal and differentiation and to identify additional therapeutic options to target bladder CSCs.