Bladder cancer stem cells: clonal origin and therapeutic perspectives.

Yi Li,Kaisu Lin,Xiaofang Quan,Xiangyang Guo,Zhao Yang,Chong Li,Ning Han

doi:10.18632/oncotarget.19112

Abstract

In this article, we review the origin and therapeutic perspectives of bladder cancer stem cells (BCSCs), which are integral to the initiation, high recurrence and chemoresistance of bladder cancer. BCSCs are heterogenous and originate from multiple cell types, including urothelial stem cells and differentiated cell types, including basal, intermediate stratum and umbrella cells. Cell surface markers, including CD44, CD67LR, EMA, ALDH1A1 and BCMab1, are used to identify and isolate BCSCs. The Hedgehog, Notch, Wnt and JAK-STAT signaling pathways play key roles in maintaining the stemness, self-renewal and proliferative potential of BCSCs. High expression of ABC transporters, acetaldehyde dehydrogenase, antioxidants and apoptosis resistance proteins in BCSCs play a critical role in chemoresistance. Consequently, a greater understanding of the biology of BCSCs will be important for identifying effective therapeutic targets to improve clinical outcomes for bladder cancer patients.

Highlights

Bladder cancer is the most common malignant tumor of urinary system with an increasing incidence [1]
We focus on the new frontiers and progress in the study of bladder cancer stem cells
Several common markers of bladder cancer stem cells (BCSCs) including CD44+, EMA, 67kDa basal layer laminin receptor (67LR)+, BCMab1+ [20, 21]are located in the basal cell layer of bladder tumor leading to more debates regarding the source of BCSCs

Summary

Introduction

Bladder cancer is the most common malignant tumor of urinary system with an increasing incidence [1]. The bladder cancer stem cells (BCSCs) are probably responsible for the high recurrence rates of bladder cancer, tumor heterogeneity and other complex biological behaviors. Cancer stem cells (CSCs) were first identified in hematopoietic malignancies as a subgroup of cells that demonstrated stemness and differentiated www.impactjournals.com/oncotarget into heterogenous populations of tumor cells [5, 6].

Results

Conclusion