Characterization of Side Populations in HNSCC: Highly Invasive, Chemoresistant and Abnormal Wnt Signaling

Song, Jun; Chang, Insoon; Chen, Zhuo; Kang, Mo K.; Wang, Cun‐Yu

doi:10.1371/journal.pone.0011456

Cited by 139 publications

(130 citation statements)

References 31 publications

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“…Previous studies have revealed that the HNSCC cell lines, M3a2 and M4e, contain SP cells that are highly tumorigenic and are involved in chemoresistance and tumor invasion (24). In accordance with these findings, the present study identified that 2.7% of the metastatic HNSCC cells were SP cells.…”

Section: Discussionsupporting

confidence: 90%

Significance of ATP-binding cassette transporter proteins in multidrug resistance of head and neck squamous cell carcinoma

et al. 2015

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Abstract. According to the cancer stem cell theory, a small subpopulation of cancer cells, known as cancer stem cells (CSCs), exist that are self-renewing and are involved in tumor invasion, metastasis and recurrence. A number of studies have reported that certain cancer cells are able to efflux the Hoechst 33342 dye. These cells are termed side population (SP) cells and share characteristic features of CSCs. The results of the present study revealed that 2.7% of primary head and neck squamous cell carcinoma (HNSCC) cells were SP cells. This was reduced to 0.7% following treatment with verapamil. The immunofluorescence and reverse transcription polymerase chain reaction analysis revealed that SP cells have an enhanced expression of the ATP-binding cassette (ABC) transporter protein ABC subfamily G, member 2 (ABCG2), which has been identified to be actively involved in drug exclusion. Similarly, the mRNA level of the oncogene B lymphoma Mo-MLV insertion region-1 and the stem cell surface proteins nestin and octamer-binding transcription factor-4 were highly expressed in the SP cells compared with the non-SP cells. In addition, it was demonstrated that HNSCC SP cells exhibited increased proliferation and were highly resistant to multiple drugs. These findings suggest that the presence of CSCs, such as SP cells, may be responsible for chemotherapy failure and tumor relapse in patients with HNSCC. Therefore, the identification of a novel therapeutic drug that could effectively target CSCs may help to eradicate refractory tumors.

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Section: Discussionsupporting

confidence: 90%

Significance of ATP-binding cassette transporter proteins in multidrug resistance of head and neck squamous cell carcinoma

et al. 2015

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“…There has been conflicting data regarding the toxicity of Hoechst 33342 dye to live cells (Montanaro et al, 2004;Platet et al, 2007). Our result showed that SP cells have almost similar proliferation rate as Non-SP cells, coupled with previous work (Huang et al, 2009;Song et al, 2010), suggesting that cytotoxicity does not account for the cancer stem-like phenotype of SP cells.…”

Section: Discussionsupporting

confidence: 52%

205 MicroRNA Expression Profiling Identifies MiR-328 Regulates Cancer Stem Cell-Like SP Cells in Colorectal Cancer

Xu¹,

Xu²,

Tong³

et al. 2012

Gastroenterology

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BACKGROUND: Side population (SP) cells and their relationship to stem cell-like properties have been insufficiently studied in colorectal cancer (CRC). MicroRNAs (miRNAs) have attracted much attention but their roles in the maintenance of SP phenotype remain unclear. METHODS: The SPs from CRC cell lines and primary cell cultures were analysed for stem cell-like properties. MiRNA microarray analysis identified miR-328 as a potential stemness miRNA of SP phenotype. The level of miR-328 expression in clinical samples and its correlation with SP fraction were determined. Gain-of-function and loss-of-function studies were performed to examine its roles in cancer stem-like SP cells. Furthermore, bioinformatics prediction and experimental validation were used to identify miR-328 target genes. RESULTS: The SP cells sorted from CRC possess cancer stem cell (CSC)-like properties, including self-renewal, differentiation, resistance to chemotherapy, invasive and strong tumour formation ability. MiR-328 expression was significantly reduced in SP cells compared with Non-SP cells (Po0.05). Moreover, miR-328 expression was downregulated in CRC (n ¼ 33, Po0.05) and low miR-328 expression tend to correlate with high SP fraction (n ¼ 15, r ¼ 0.6559, Po0.05, Pearson's correlation). Functional studies indicated that miR-328 expression affects the number of SP cells. In addition, miR-328 overexpression reversed drug resistance and inhibited cell invasion of SP cells. Furthermore, luciferase reporter assay demonstrated that miR-328 directly targets ABCG2 and MMP16 and affects the levels of mRNA and protein expression in SP cells. CONCLUSION: These findings indicate that CRC contain cancer stem-like SP cells. MiR-328 has an important role in maintaining cancer stem-like SP phenotype that may be a potential target for effective CRC therapy.

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“…The most frequently applied method for identifying CSCs is flow cytometry, which detects cells with the ability to excrete the vital DNA dye Hoechst 33342 (34)(35)(36)(37)(38). A distinctive small non-dyed population of cells, termed the side population (SP), has been detected in numerous tumors, and is highly tumorigenic (39)(40)(41)(42)(43)(44).…”

Section: Concept and Identification Of Cscsmentioning

confidence: 99%

Expression of SOX2 in oral squamous cell carcinoma and the association with lymph node metastasis

Ren

Zhang

2016

Oncology Letters

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Abstract. Oral squamous cell carcinomas (OSCCs) are a growing problem in the world. The various existing treatments have not markedly improved the survival rate of patients with OSCC during the past three decades. Novel treatment strategies are required. Sex determining region Y-box 2 (SOX2) is a transcription factor that is involved in the maintenance of embryonic stem cell pluripotency and in multiple developmental processes. SOX2 expression was indicated to act as a prognostic factor in various types of tumors, including breast, colorectal, gastric and lung cancer and glioblastoma, and as a link between malignancy and stemness. Cancer stem cells (CSCs) may be responsible for the genesis, growth and metastatic spread of tumors. The poor survival outcomes for OSCC patients may be attributable to a poor selection of target cells for treatment, as current oral cancer therapies are generally aimed at the global mass of tumor. Therefore, the consideration that novel approaches to oral cancer may be targeted using SOX2 and CSCs appears reasonable. In order to better understand the oncogenic roles and the corresponding signal transduction pathways of the SOX2 protein, the present study emphasizes the role of SOX2 in OSCC, including the proteins associated with OSCC, and reviews the literature regarding the role of SOX2 in lymph node metastasis. The aim of the present study is to provide a reference for future studies that engage in research on the aforementioned subject.

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Characterization of Side Populations in HNSCC: Highly Invasive, Chemoresistant and Abnormal Wnt Signaling

Cited by 139 publications

References 31 publications

Significance of ATP-binding cassette transporter proteins in multidrug resistance of head and neck squamous cell carcinoma

Significance of ATP-binding cassette transporter proteins in multidrug resistance of head and neck squamous cell carcinoma

205 MicroRNA Expression Profiling Identifies MiR-328 Regulates Cancer Stem Cell-Like SP Cells in Colorectal Cancer

Expression of SOX2 in oral squamous cell carcinoma and the association with lymph node metastasis

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