Spheres derived from the human SK-RC-42 renal cell carcinoma cell line are enriched in cancer stem cells

Zhong, Yong; Guan, Kaopeng; Guo, Sujuan; Zhou, Chunxia; Wang, Dongmei; Ma, Wenbo; Zhang, Youhui; Li, Changling; Zhang, Shuren

doi:10.1016/j.canlet.2010.08.013

Cited by 115 publications

(104 citation statements)

References 52 publications

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“…3A, 3B). Similarly, reduction of CD105-expressing cells after sphere formation was observed by Zhong et al [23] in another RCC cell line. Interestingly, this loss of CD105 expression was reversed in RCC-26 and SK-RC-17 cells when sphere cells were cultivated under adherent growth conditions for 3 days (Fig.…”

Section: Cxcr4mentioning

confidence: 68%

“…In order to be able to monitor the efficiency of such therapies, CSCs must be reliably identified using suitable markers. Although surface expression of CD105 has been used to enrich for tumor-initiating cells in RCC [19,24], this marker was not suitable for use in all RCC cell lines to identify CSC ( [23] and this work).…”

Section: Discussionmentioning

confidence: 99%

“…Addla et al [22] characterized a Hoechst 33342 dye side population in malignant renal epithelial cells derived from primary RCC which were enriched for cells with high proliferative capacity and stem cell-like properties. In addition, cultivation of cells from a RCC cell line as spheres enriched a cell population which exhibited many features of CSCs, including higher expression of stemness genes and resistance to chemotherapeutic agents, as well as stronger tumorigenicity in comparison to adherently growing parental cells [23]. Furthermore, CD105 which is present on normal renal mesenchymal stem cells was used to enrich cells with stem cell characteristics from primary RCC.…”

Section: Introductionmentioning

confidence: 99%

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CXC Chemokine Receptor 4 is Essential for Maintenance of Renal cell Carcinoma-Initiating Cells and Predicts Metastasis

et al. 2013

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In many solid tumors, cancer stem cells (CSC) represent a population with tumor-initiating, self-renewal, and differentiation potential, which can be identified by surface protein markers. No generally applicable markers are yet known for renal cell carcinoma (RCC). Two RCC cell lines (RCC-26, RCC-53) were found to differ widely in their capacity to form spheres in vitro and to establish tumors in mice, potentially reflecting differences in CSC content. A subpopulation expressing the CXC chemokine receptor 4 (CXCR4) was present only in the more tumorigenic cell line RCC-53. When grown as spheres, most of the RCC-53 cells were CXCR4-positive, expressed stem cell-associated transcription factor genes at elevated levels, and were more resistant toward the tyrosine kinase inhibitors sunitinib, sorafenib, and pazopanib. Sorted CXCR4-positive cells exhibited greater capacity for sphere formation and tumor growthinducing potential in vivo than CXCR4-negative cells. Significantly, higher CXCR4 mRNA levels in primary RCC tumors from patients with localized but not disseminated disease predicted shorter survival. Downregulation of CXCR4 expression by small interfering RNA (siRNA) or pharmacological inhibition by AMD3100 compromised tumor sphere formation, viability of CXCR4-positive cells, and increased their responsiveness toward tyrosine kinase inhibitors. In conclusion, CXCR4 identifies a subpopulation of tumor-initiating cells in RCC cell lines and plays a role in their maintenance. The relative insensitivity of such cells to tyrosine kinase inhibitors might contribute to the development of therapy resistance in RCC patients. Future therapies therefore could combine blockade of the CXCR4 signaling pathway with standard therapies for more effective treatments of metastatic RCC.

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Section: Cxcr4mentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CXC Chemokine Receptor 4 is Essential for Maintenance of Renal cell Carcinoma-Initiating Cells and Predicts Metastasis

et al. 2013

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“…A number of studies have isolated pools of TICs from RCC cell lines and tumor specimens (9)(10)(11)(12)(13)(14). RCC TICs appear to be responsible for malignancy progression, relapse and metastasis (8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Tumor-initiating cells contribute to radiation resistance in primary human renal clear cell carcinomas by activating the DNA damage checkpoint response

Gao

et al. 2017

Oncology Letters

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Abstract. The use of radiotherapy in patients with clear cell renal carcinoma (ccRCC) is predominantly limited to palliation of metastases or control of local growth, because ccRCC cells readily develop radioresistance. The mechanisms underlying ccRCC resistance remain elusive. The present study demonstrated that ccRCC cells that survive fractionated radiation treatment display tumor-initiating cell (TIC) characteristics, such as high self-renewal and tumorigenic capacities, and overexpress stemness genes. ccRCC cells that survived fractionated radiation exhibited increased activation of the DNA damage checkpoint response and G2/M phase arrest compared with sham-irradiated cells. The results of the present study suggest that ionizing radiation destroys the bulk of tumor cells within ccRCC, but spares TICs; this subpopulation confers ccRCC radioresistance and may cause tumor recurrence or relapse following radiotherapy. Furthermore, these findings indicate that the DNA damage checkpoint response may serve as a potential therapeutic target for overcoming resistance of TICs in patients with ccRCC.

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“…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).…”

mentioning

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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Spheres derived from the human SK-RC-42 renal cell carcinoma cell line are enriched in cancer stem cells

Cited by 115 publications

References 52 publications

CXC Chemokine Receptor 4 is Essential for Maintenance of Renal cell Carcinoma-Initiating Cells and Predicts Metastasis

CXC Chemokine Receptor 4 is Essential for Maintenance of Renal cell Carcinoma-Initiating Cells and Predicts Metastasis

Tumor-initiating cells contribute to radiation resistance in primary human renal clear cell carcinomas by activating the DNA damage checkpoint response

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

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