Aldehyde Dehydrogenase 1 Identifies Cells with Cancer Stem Cell-Like Properties in a Human Renal Cell Carcinoma Cell Line

Ueda, Kosuke; Ogasawara, Satoshi; Akiba, Jun; Nakayama, Masamichi; Todoroki, Keita; Ueda, Kenichi; Sanada, Sakiko; Suekane, Shigetaka; Noguchi, Masanori; Matsuoka, Kei; Yano, Hirohisa

doi:10.1371/journal.pone.0075463

Cited by 78 publications

(90 citation statements)

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“…At present, the sorting methods of CSCs include flow cytometry based on special cell surface markers, the side population cell sorting technique, tumor sphere culturing and the ALDEFLUOR™ assay (6)(7)(8)(9). Previous studies have identified the CSCs from colon, breast and glioblastoma cancer, as well as other cancer cell lines, using the sphere culturing method (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Spheres from cervical cancer cells display stemness and cancer drug resistance

Liu

Wang

et al. 2016

Oncology Letters

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Abstract. Cervical cancer is one of the most common gynecological malignant tumors and is the cause of a serious health problem worldwide. An increasing amount of evidence has shown that cancer stem cells (CSCs) are present in tumors, and that these CSCs may be responsible for tumor metastasis and relapse. The present study aimed to identify and characterize a CSC population from the CaSki cell line. First, a stem cell culture medium was used to selectively expand the cancer stem-like cell spheres, and the putative stemness markers, Oct4 and Sox2, were identified. These markers were all highly expressed in the CaSki sphere-forming cells. Next, target region amplified polymorphism-polymerase chain reaction was performed and the CaSki sphere-forming cells were found to exhibit higher telomerase activity than the CaSki control cells cultured in non-stem cell medium. Using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, it was found that the CaSki sphere-forming cells were more resistant to chemotherapeutic drugs than the control CaSki cells. Using the tumor invasive assay, it was shown that the CaSki sphere-forming cells were more invasive than the control CaSki cells. These characteristics all suggested that the tumor sphere-forming cells mirrored the acknowledged CSC phenotypes. Overall, the use of a suspended sphere culture of CaSki cells may be an easy and feasible approach for enriching cancer stem-like cells in cervical cancer research.

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Section: Introductionmentioning

confidence: 99%

Spheres from cervical cancer cells display stemness and cancer drug resistance

Liu

Wang

et al. 2016

Oncology Letters

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“…Compared with non-SP RCC cells, the SP is distinguishable by increased sphere-forming ability in vitro , enhanced proliferative potential, and greater expression levels of β-catenin, Sonic Hedgehog, Notch, and Pax-2 stem cell markers. Furthermore, the SP had an abundance of ALDH-positive cells, suggesting that ALDH enzymatic activity may be associated with the SP (Ueda et al, 2013). DNAJB8 knockout cells displayed a decreased ratio of SP to non-SP cells and reduced sphere-forming ability, indicating that DNAJB8 contributes to CSC-like phenotype of RCC (Nishizawa et al, 2012).…”

Section: Intracellular Markers In Renal Cscsmentioning

confidence: 99%

Targeting Strategies for Renal Cell Carcinoma: From Renal Cancer Cells to Renal Cancer Stem Cells

Yuan

GuiXian

et al. 2016

Front. Pharmacol.

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Renal cell carcinoma (RCC) is a common form of urologic tumor that originates from the highly heterogeneous epithelium of renal tubules. Over the last decade, targeting therapies to renal cancer cells have transformed clinical care for RCC. Recently, it was proposed that renal cancer stem cells (CSCs) isolated from renal carcinomas were responsible for driving tumor growth and resistance to conventional chemotherapy and radiotherapy, according to the theory of CSCs; this has provided the rationale for therapies targeting this aggressive cell population. Precise identification of renal CSC populations and the complete cell hierarchy will accurately inform characterization of disease subtypes. This will ultimately contribute to more personalized and targeted therapies. Here, we summarize potential targeting strategies for renal cancer cells and renal CSCs, including tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors (mTOR), interleukins, CSC marker inhibitors, bone morphogenetic protein-2, antibody drug conjugates, and nanomedicine. In conclusion, targeting therapies for RCC represent new directions for exploration and clinical investigation and they plant a seed of hope for advanced clinical care.

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“…Importantly, in the metastatic RCC cell lines, ALDH high cells formed about 15% of the total number of cells and had higher sphere-forming capacity, self-renewal ability, and tumorigenicity than ALDH low cells. While anther study showed that ALDH gene expression was correlated with tumor grade but not with tumor stage in patients with RCC (16). Overall pooled analysis suggested that high CSCs markers, including CD133, CD44, CXCR4 and CD105, expression predicted poor overall survival, cancer-specific survival, disease-free survival and progression-free survival (17).…”

Section: Introductionmentioning

confidence: 99%

CBFA2T2 is Associated with a Cancer Stem Cell State in Renal Cell Carcinoma

Chen¹,

Liang²,

Wang³

et al. 2017

Preprint

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Renal cell carcinoma (RCC) is the most common kidney cancer, accounting for approximately 80-90 % of all primary kidney cancer. Treatment for patients with advanced RCC remains unsatisfactory. Rare cancer stem cells (CSCs) are proposed to be responsible for failure of current treatment. Here, we investigate the effects of CBFA2T2 on CSCs regulation in RCC, as well as to elucidate the possible mechanisms. We showed that CBFA2T2 expression can significantly predict the survival of RCC patients. Functional assays showed that knocking-down of CBFA2T2 can inhibit cell migration and invasion in 786-O and A-498 cells in vitro, and reduce ALDH high CSCs populations. Furthermore, CBFA2T2 expression is necessary for sphere-forming ability and cancer stem cells marker expression in RCC cell lines. Collectively, our data suggest that CBFA2T2 expression correlates with aggressive characteristics of RCC and CBFA2T2 is required for maintenance of "stemness" through regulation of stem cells factors, thereby highlighting CBFA2T2 as a potential therapeutic target for RCC treatment.KEYWORDS: CBFA2T2; renal cell carcinoma; cancer stem cells; OCT-4; NANOG INTRODUCTIONRenal cell carcinoma (RCC) represents one of the most common type of renal cancer, accounting for 90% of adult renal malignancies (1). The prognosis of advanced RCC is very poor, with a 5-year survival rate of 5-10% (2). In addition, around 20-40% of RCC patients developed recurrence after treatment (3). The mechanisms of how these metastasis and recurrence occur are largely uncharacterized. Recent studies have shown the presence of cancer stem cells (CSCs) in various solid tumor tissues (4-6). CSCs are undifferentiated multipotential tumor cells that have high tumorigenic activity and the capacity to self-renew (4, 5, 7). Moreover, CSCs promote cancer resistance to treatment and recurrence, leading to high mortality (5). Therefore, CSC-targeted therapy can be an essential part of cancer therapy.Previously, CSCs in RCC have been identified by using either stem cell markers (CD133, CD44, CXCR4 and CD105) (8-11) or functional assays (sphere-forming ability, side population and ALDH activity) (12)(13)(14). Especially, in RCC cell lines, ALDH high cells showed CSC properties in vitro, such as clonogenic and self-renewal ability and increased expression of OCT4 and NANOG (15). Importantly, in the metastatic RCC cell lines, ALDH high cells formed about 15% of the total number of cells and had higher Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted:

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Aldehyde Dehydrogenase 1 Identifies Cells with Cancer Stem Cell-Like Properties in a Human Renal Cell Carcinoma Cell Line

Cited by 78 publications

References 50 publications

Spheres from cervical cancer cells display stemness and cancer drug resistance

Spheres from cervical cancer cells display stemness and cancer drug resistance

Targeting Strategies for Renal Cell Carcinoma: From Renal Cancer Cells to Renal Cancer Stem Cells

CBFA2T2 is Associated with a Cancer Stem Cell State in Renal Cell Carcinoma

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