Urology, Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
Curr Opin Urol. 2010 Sep;20(5):393-7. doi: 10.1097/MOU.0b013e32833cc9df.
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.
目的综述：最近，从各种人类恶性肿瘤中分离和鉴定癌症干细胞（CSCs）的前瞻性研究表明，CSCs 对放疗和化疗具有抗性。因此，CSCs 可能是治疗干预的“根源”和理想靶点。在这里，我们将重点回顾膀胱癌干细胞的历史观点、最近的文献及其临床意义。
最新发现：基于细胞表面受体、细胞角蛋白标志物、药物转运体的表达以及 Hoechst 33,342 染料（侧群）的有效外排，已经从患者标本、建立的癌细胞系和异种移植中前瞻性地分离出 CSCs。此外，CSCs 的全基因组表达谱分析显示，CSCs 的激活基因特征与侵袭性膀胱癌相似，支持肿瘤细胞亚群有助于膀胱癌进展的观点。最后，我们使用针对 CD47 的阻断抗体在体外和异种移植中对膀胱 CSCs 的临床前靶向研究显示出有希望的疗效。
总结：在人类膀胱癌中存在功能不同的 CSCs，并且可以进行前瞻性分离。继续研究对于确定其起源细胞、维持自我更新和分化的程序以及确定针对膀胱 CSCs 的其他治疗选择非常重要。
