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

Urology, Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
Current opinion in urology (Impact Factor: 2.33). 09/2010; 20(5):393-7. DOI: 10.1097/MOU.0b013e32833cc9df
Source: PubMed
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.

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    • "Although both CIS and papillary lesions belong to superficial urothelial carcinomas, they show different morphologies as well as invasive potentials. Therefore, it has been suggested that CIS and papillary lesions arise from different cell types or harbor distinct mutations [4][5][6][7][8][9][10][11][12][13][14][15][16]. Indeed, supportive evidence has shown that both CIS and invasive urothelial carcinoma arise from basal cells, whereas intermediate cells serve as the progenitors of papillary carcinomas [17]. "
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    • "This receptor is strongly overexpressed in several cancer types including both hematological and solid tumors[80,91,109,110]. A high CD47 expression has been a poor prognostic factor for patients with these diseases[80,111,112]. CD47 is also highly expressed in tumor initiating cells (TICs) or cancer stem cells (CSC) where it is a marker of more aggressive tumor cells, with higher metastatic potential, and less sensitive to engulfment by macrophages, thereby escaping from immune surveillance while increasing cell proliferation through activation of the PI3K/Akt pathway[92,113114115116. Therefore, CD47 becomes an attractive target for therapeutic approaches with both antitumor and antiinflammatory properties and anti-CD47 antibodies are being tested with positive results in preclinical and clinical settings[80,111,112,117]. "
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    • "Recent clinical studies have demonstrated that immune checkpoint inhibition, which restores anti-tumor T-cell immunity, is associated with a beneficial objective response and remarkably improves the prognosis of patients with advanced malignancies, including patients with BC [138]. Chan et al. reported another potential type of immunotherapy against BC, where bladder CSCs express higher levels of CD47, a cell surface protein that provides an inhibitory signal for macrophage phagocytosis, compared with the rest of the tumor [20,139]. Blockade of CD47 with a monoclonal antibody resulted in macrophage engulfment of BC cells in vitro, suggesting that immunotherapy against CD47 could be effective in the treatment of MIBC. "
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