Identification of side population cells from bladder cancer cells by DyeCycle Violet staining

She, Jun; Zhang, Peng Ge; Wang, Zi Ming; Wang, Gan; Xiang, Ming

doi:10.4161/cbt.7.10.6637

Cited by 58 publications

(50 citation statements)

References 27 publications

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“…Such a T-IC population exists at the top of a hierarchical relationship and is capable of reconstituting all downstream populations. These results add complexity to our originally proposed T-IC model (19) and suggest BC conforms to the cancer stem cell model (19,(28)(29)(30)(31)(32)(33).…”

Section: Discussionmentioning

confidence: 59%

Three differentiation states risk-stratify bladder cancer into distinct subtypes

Volkmer

Sahoo

Chin³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

238

236

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Current clinical judgment in bladder cancer (BC) relies primarily on pathological stage and grade. We investigated whether a molecular classification of tumor cell differentiation, based on a developmental biology approach, can provide additional prognostic information. Exploiting large preexisting gene-expression databases, we developed a biologically supervised computational model to predict markers that correspond with BC differentiation. To provide mechanistic insight, we assessed relative tumorigenicity and differentiation potential via xenotransplantation. We then correlated the prognostic utility of the identified markers to outcomes within gene expression and formalin-fixed paraffin-embedded (FFPE) tissue datasets. Our data indicate that BC can be subclassified into three subtypes, on the basis of their differentiation states: basal, intermediate, and differentiated, where only the most primitive tumor cell subpopulation within each subtype is capable of generating xenograft tumors and recapitulating downstream populations. We found that keratin 14 (KRT14) marks the most primitive differentiation state that precedes KRT5 and KRT20 expression. Furthermore, KRT14 expression is consistently associated with worse prognosis in both univariate and multivariate analyses. We identify here three distinct BC subtypes on the basis of their differentiation states, each harboring a unique tumor-initiating population.

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Section: Discussionmentioning

confidence: 59%

Three differentiation states risk-stratify bladder cancer into distinct subtypes

Volkmer

Sahoo

Chin³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

238

236

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“…Multiple groups have used this approach to identify and isolate urothelial CSCs. She and colleagues showed that side population cells isolated from bladder cancer cell lines have selfrenewing ability, clonogenic capacity, and can initiate tumor formation when subcutaneously injected in low numbers (1 Â 10 3 ) into immunocompromised mice (36). Furthermore, expression of the ABC transporters ABCG2 and ABCB1 (also known as MDR1) was confirmed, and side population cells express the stem cell markers POU5F1 and BMI1, implying a stem-like phenotype of side population cells (36).…”

Section: Urothelial Stem Cellsmentioning

confidence: 99%

“…She and colleagues showed that side population cells isolated from bladder cancer cell lines have selfrenewing ability, clonogenic capacity, and can initiate tumor formation when subcutaneously injected in low numbers (1 Â 10 3 ) into immunocompromised mice (36). Furthermore, expression of the ABC transporters ABCG2 and ABCB1 (also known as MDR1) was confirmed, and side population cells express the stem cell markers POU5F1 and BMI1, implying a stem-like phenotype of side population cells (36). In an independent study, side population cells isolated from the T24 bladder cancer cell line showed a more quiescent cell state, asymmetric cell division, rapid cell growth, and colony formation and chemo-and radioresistance, providing further evidence for CSC enrichment (37).…”

Section: Urothelial Stem Cellsmentioning

confidence: 99%

Epithelial Plasticity, Cancer Stem Cells, and the Tumor-Supportive Stroma in Bladder Carcinoma

Horst

Bos

Pluijm

2012

Molecular Cancer Research

139

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High recurrence rates and poor survival rates of metastatic bladder cancer emphasize the need for a drug that can prevent and/or treat bladder cancer progression and metastasis formation. Accumulating evidence suggests that cancer stem/progenitor cells are involved in tumor relapse and therapy resistance in urothelial carcinoma. These cells seem less affected by the antiproliferative therapies, as they are largely quiescent, have an increased DNA damage response, reside in difficult-to-reach, protective cancer stem cell niches and express ABC transporters that can efflux drugs from the cells. Recent studies have shown that epithelial-to-mesenchymal transition (EMT), a process in which sessile, epithelial cells switch to a motile, mesenchymal phenotype may render cancer cells with cancer stem cells properties and/or stimulate the expansion of this malignant cellular subpopulation. As cancer cells undergo EMT, invasiveness, drug resistance, angiogenesis, and metastatic ability seem to increase in parallel, thus giving rise to a more aggressive tumor type. Furthermore, the tumor microenvironment (tumor-associated stromal cells, extracellular matrix) plays a key role in tumorigenesis, tumor progression, and metastasis formation. Taken together, the secret for more effective cancer therapies might lie in developing and combining therapeutic strategies that also target cancer stem/progenitor cells and create an inhospitable microenvironment for highly malignant bladder cancer cells. This review will focus on the current concepts about the role of cancer stem cells, epithelial plasticity, and the supportive stroma in bladder carcinoma. The potential implications for the development of novel bladder cancer therapy will be discussed. Mol Cancer Res; 10(8); 995-1009. Ó2012 AACR. Bladder CancerWorldwide, an estimated number of 386,300 new cases and 150,200 deaths from bladder cancer occurred in 2008, with the majority of cases (77%) occurring in men. Thereby, bladder cancer is the seventh most common cancer and the ninth most common cause of cancer-related death in men. Bladder cancer is most common in developed countries, where 63% of the cases occurred in 2002. In Europe and the United States, for example, bladder cancer is the fourth most common cancer in males. Overall, the 5-year survival rate of bladder cancer is approximately 80%, and it varies with the stage of the tumor, ranging from 97% for carcinoma in situ to 6% for metastatic disease.Urothelial carcinoma is a heterogeneous disease and multifocal tumors can develop in the same patient. Multifocality can be explained by the monoclonal theory, that is, multiple tumors arise from a single transformed cell or by the field cancerization theory (1). In the latter, exposure of the urothelium to important risk factors for bladder cancer, such as occupational carcinogens induces changes at different sites of the urothelium. As described by Cheng and colleagues (1), urothelial carcinoma in situ is a well-established precursor of invasive bladder cancer and may be...

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“…There was no correlation between the proportion of SP-cells and the transformation status of the respective cell line. Strikingly, Dye cycle Violet purified non-SP cells could, upon further sub-culturing, generate a small proportion of SP cells and the authors exclude the possibility of contamination [24]. Moreover, in the bladder carcinoma cell line J82, cell cultures founded by purified SP cells displayed a sharp drop in the SP fraction immediately after seeding (i.e.…”

mentioning

confidence: 98%

“…Both Hoechst 33342 and Dye Cycle Violet have been used and both staining procedures were able to enrich for clonogenic and tumorigenic cells [22][23][24]. Surprisingly, a side-by-side comparison of both stains revealed that in some urothelial cancer cell lines, the proportion of SP cells detected by the Dye Cycle Violet staining could be far higher (up to 20 times) than for the Hoechst 33342 (e.g.…”

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confidence: 99%

Stem cells in the biology of normal urothelium and urothelial carcinoma

Hatina¹,

Schulz²

2012

neo

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Urothelium is a special type of stratified epithelium that lines the distal portion of the urinary tract. For a long time, basal urothelial cells have been suspected to include a population of urothelial stem cells. Recent experiments identifying label-retaining cells as well as lineage tracing analyses corroborate this notion. There are striking morphological and antigenic similarities between basal or differentiated urothelial cells and the corresponding cells in some urothelial carcinomas. In this respect, basal cell-specific markers provide good candidates to identify urothelial carcinoma stem cells, e.g. specific cytokeratins (CK5, CK14, CK17) or adhesion molecules (specific integrin subspecies, CD44). Common properties of the stem cells of normal urothelium and urothelial cancer have thus emerged. Both are characterized by a remarkable plasticity and both rely on reciprocal interactions with stromal fibroblasts. However, the stem cells of individual urothelial carcinomas appear to differ considerably and may contribute to the heterogeneity of this disease. The presence, quantity, and particular biological nature of urothelial carcinoma stem cells in each case may thus carry important clinical information that might allow a rationale stratification of urothelial cancer patients for treatment in the near future.

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Identification of side population cells from bladder cancer cells by DyeCycle Violet staining

Abstract: Side population (SP) cells can be used to identify putative cancer stem cells (CSC), but this technique is

Cited by 58 publications

References 27 publications

Three differentiation states risk-stratify bladder cancer into distinct subtypes

Three differentiation states risk-stratify bladder cancer into distinct subtypes

Epithelial Plasticity, Cancer Stem Cells, and the Tumor-Supportive Stroma in Bladder Carcinoma

Stem cells in the biology of normal urothelium and urothelial carcinoma

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