Biological characteristics of Rh123high stem-like cells in a side population of 786-O renal carcinoma cells

Lü, Jing; Cui, Yong; Zhu, Jianwei; He, Jié; Zhou, Guangming; Yue, Zhongjin

doi:10.3892/ol.2013.1270

Cited by 24 publications

(31 citation statements)

References 14 publications

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“…Most of this evidence is based on tumor-tissue-specific SCLCCs, while some are based on RCC cell lines [18–20, 42, 43]. SCLCCs have been identified from RCC cell lines based on chemokine receptor CXCR4 [19, 42] and side population cell selection by aldehyde dehydrogenase activity [18, 20, 43], Hoechst 33342 dye [44] and rhodamine 123 [45]. Previously, Bussolati et al observed renal carcinoma specimens from patients after radical nephrectomy, which showed CD105+ subpopulation is enrich for tumor-initiating cells (TICs) [31] and tumor angiogenesis [46].…”

Section: Discussionmentioning

confidence: 99%

Comparative Gene Expression Profiling of Primary and Metastatic Renal Cell Carcinoma Stem Cell-Like Cancer Cells

et al. 2016

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BackgroundRecent advancement in cancer research has shown that tumors are highly heterogeneous, and multiple phenotypically different cell populations are found in a single tumor. Cancer development and tumor growth are driven by specific types of cells—stem cell-like cancer cells (SCLCCs)—which are also responsible for metastatic spread and drug resistance. This research was designed to verify the presence of SCLCCs in renal cell cancer cell lines. Subsequently, we aimed to characterize phenotype and cell biology of CD105+ cells, defined previously as renal cell carcinoma tumor-initiating cells. The main goal of the project was to describe the gene-expression profile of stem cell-like cancer cells of primary tumor and metastatic origin.Materials and MethodsReal-time PCR analysis of stemness genes (Oct-4, Nanog and Ncam) and soft agar colony formation assay were conducted to check the stemness properties of renal cell carcinoma (RCC) cell lines. FACS analysis of CD105+ and CD133+ cells was performed on RCC cells. Isolated CD105+ cells were verified for expression of mesenchymal markers—CD24, CD146, CD90, CD73, CD44, CD11b, CD19, CD34, CD45, HLA-DR and alkaline phosphatase. Hanging drop assay was used to investigate CD105+ cell-cell cohesion. Analysis of free-floating 3D spheres formed by isolated CD105+ was verified, as spheres have been hypothesized to contain undifferentiated multipotent progenitor cells. Finally, CD105+ cells were sorted from primary (Caki-2) and metastatic (ACHN) renal cell cancer cell lines. Gene-expression profiling of sorted CD105+ cells was performed with Agilent’s human GE 4x44K v2 microarrays. Differentially expressed genes were further categorized into canonical pathways. Network analysis and downstream analysis were performed with Ingenuity Pathway Analysis.ResultsMetastatic RCC cell lines (ACHN and Caki-1) demonstrated higher colony-forming ability in comparison to primary RCC cell lines. Metastatic RCC cell lines harbor numerous CD105+ cell subpopulations and have higher expression of stemness genes (Oct-4 and Nanog). CD105+ cells adopt 3D grape-like floating structures under handing drop conditions. Sorted CD105+ cells are positive for human mesenchymal stem cell (MSC) markers CD90, CD73, CD44, CD146, and alkaline phosphatase activity, but not for CD24 and hematopoietic lineage markers CD34, CD11b, CD19, CD45, and HLA-DR. 1411 genes are commonly differentially expressed in CD105+ cells (both from primary [Caki-2] and metastatic RCC [ACHN] cells) in comparison to a healthy kidney epithelial cell line (ASE-5063). TGF-β, Wnt/β-catenine, epithelial-mesenchymal transition (EMT), Rap1 signaling, PI3K-Akt signaling, and Hippo signaling pathway are deregulated in CD105+ cells. TGFB1, ERBB2, and TNF are the most significant transcriptional regulators activated in these cells.ConclusionsAll together, RCC-CD105+ cells present stemlike properties. These stem cell-like cancer cells may represent a novel target for therapy. A unique gene-expression profile of CD105+ cells could be used as initia...

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Section: Discussionmentioning

confidence: 99%

Comparative Gene Expression Profiling of Primary and Metastatic Renal Cell Carcinoma Stem Cell-Like Cancer Cells

et al. 2016

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“…The ACHN line CSC subpopulation is Hoechst33342-negative and ALDH-positive [98], while Caki-2 CSCs are also ALDH-positive and form spheres [99]. The 786-O cell line is also shown to bear the CSC subpopulation, as confirmed by Rh123 fluorescent intensity based isolation [105]. At the same time, SK-RC-42 cells cultured in spheres have features of CSCs [90].…”

Section: Introductionmentioning

confidence: 99%

Choosing the right cell line for renal cell cancer research

Brodaczewska¹,

Szczylik²,

et al. 2016

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Cell lines are still a tool of choice for many fields of biomedical research, including oncology. Although cancer is a very complex disease, many discoveries have been made using monocultures of established cell lines. Therefore, the proper use of in vitro models is crucial to enhance our understanding of cancer. Therapeutics against renal cell cancer (RCC) are also screened with the use of cell lines. Multiple RCC in vitro cultures are available, allowing in vivo heterogeneity in the laboratory, but at the same time, these can be a source of errors. In this review, we tried to sum up the data on the RCC cell lines used currently. An increasing amount of data on RCC shed new light on the molecular background of the disease; however, it revealed how much still needs to be done. As new types of RCC are being distinguished, novel cell lines and the re-exploration of old ones seems to be indispensable to create effective in vitro tools for drug screening and more.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-016-0565-8) contains supplementary material, which is available to authorized users.

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“…Based on Rh123 staining, RCC cells were characterized as Rh123 high and Rh123 low cells in a recent study [39]. Serially transplanted Rh123 high cells into SCID mice were able to form tumours in all cases (12/12 cases).…”

Section: Introductionmentioning

confidence: 99%

Metastasis-Initiating Cells in Renal Cancer

Khan¹,

Czarnecka²,

Duchnowska³

et al. 2014

CST

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Metastasis is a complex process that propagates cells from the primary or initial site of the cancer occurrence to distant parts of the body. Cancer cells break from the cancer site and circulate through the bloodstream or lymph vessels, allowing them to reach nearly all parts of the body. These circulating tumour cells (CTCs) contain specialized metastasis-initiating cells (MICs) that reside in the biological heterogeneous primary tumour. Researchers have hypothesized that metastasis of renal cell carcinoma is initiated by circulation of MICs in patients’ blood and bone marrow. Based on the cancer stem/progenitor cell concept of carcinogenesis, understanding the molecular phenotypes of metastasis-initiating cells (MICs) in renal cancer could play a vital role in developing strategies for therapeutic interventions in renal cancer. Existence of MICs among CTCs in renal carcinoma has not been proven in large scale. However, some studies have reported that specialized markers are found on the surface of circulating cells from the primary tumour. In mice, MICs have been isolated from CTCs using such markers, which have then been transplanted into xenograft model to show whether they give rise to metastasis in different organs. Considering these findings, in this review we have attempted to summarize the studies connected with MICs and their gene expression profiles that are responsible for metastasis in renal cancer.

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Biological characteristics of Rh123high stem-like cells in a side population of 786-O renal carcinoma cells

Cited by 24 publications

References 14 publications

Comparative Gene Expression Profiling of Primary and Metastatic Renal Cell Carcinoma Stem Cell-Like Cancer Cells

Comparative Gene Expression Profiling of Primary and Metastatic Renal Cell Carcinoma Stem Cell-Like Cancer Cells

Choosing the right cell line for renal cell cancer research

Metastasis-Initiating Cells in Renal Cancer

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