Identification of CD24 as a Cancer Stem Cell Marker in Human Nasopharyngeal Carcinoma

Yang, Cheng; Wang, Huiling; Lin, Yi‐Sheng; Kumar, Krishan; Lin, Herng Ching; Chang, Chih-Jung; Lu, Cuihua; Huang, Tzu Ting; Martel, Jan; Ojcius, David M.; Chang, Yu‐Sun; Young, John Ding‐E; Lai, Hsin‐Chih

doi:10.1371/journal.pone.0099412

Cited by 50 publications

(41 citation statements)

References 59 publications

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“…The lower expressions of c-myc, Nanog, Oct3/4, Sox2, and EpCAM in β-catenin-silenced cells suggested that the production of CSC was suppressed. The enrichment of Sox2 in CSC-like population in NPC has already been reported, and Sox2 has also found to be involved in regulating the growth of the CSC-like population in NPC [4,35]. In the present study, we demonstrated that silencing β-catenin would inversely influence the expression of Sox2 both in vitro and in vivo.…”

Section: β-Catenin Is Necessary For Maintaining Characteristics Of Cssupporting

confidence: 81%

β-Catenin is important for cancer stem cell generation and tumorigenic activity in nasopharyngeal carcinoma

Jiang

Niu

Huang

et al. 2016

ABBS

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Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors with poor prognosis and recurrence in South China. The hard eradication of NPC in clinic is predominantly due to cancer stem cells (CSCs). Increasing evidence revealed that the aberrant activation of Wnt/β-catenin was positively correlated with the produce of CSCs. To further investigate the effect of β-catenin on CSCs and tumorigenesis in NPC, a CNE2 cell line ( pLKO.1-sh-β-catenin-CNE2) with stably suppressed expression of β-catenin was used in this study. The expressions of biomarkers in CSCs including c-myc, Nanog, Oct3/4, Sox2, EpCAM as well as adhesion-related proteins like E-cadherin and vimentin were analyzed by western blot analysis and immunofluorescent staining. The proliferation and migration abilities were investigated by MTT assay and Transwell assay, respectively. Cell cycle was analyzed by flow cytometry. Finally, xenograft was performed to determine the effect of β-catenin on oncogenesis in vivo. Results showed that the expressions of c-myc, Nanog, Oct3/4, Sox2, and EpCAM were all decreased in pLKO.1-sh-β-catenin-CNE2 cells. It was also found that vimentin was downregulated, while E-cadherin was upregulated. Results of MTT and Transwell assays suggested that the proliferation and migration abilities were impaired by silencing of β-catenin, and more cells were arrested in G1 phase when compared with the control. In vivo study indicated that the tumor growth was markedly suppressed in experimental group. Based on current findings, β-catenin may function as an essential protein for the maintenance of migration and proliferation abilities of NPC cells, and a complicated network consisting of c-myc, Nanog, Oct3/4, Sox2, EpCAM, E-cadherin, vimentin, and β-catenin may be involved in the inherent regulation mechanisms.

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Section: β-Catenin Is Necessary For Maintaining Characteristics Of Cssupporting

confidence: 81%

β-Catenin is important for cancer stem cell generation and tumorigenic activity in nasopharyngeal carcinoma

Jiang

Niu

Huang

et al. 2016

ABBS

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“…In human nasopharyngeal carcinoma cell lines, cells with higher CD24 C expression have increased growth and tumor sphere formation in vitro. 36 While previous studies look at the role of CD24 in the tumors, our investigation turned to analysis of CD24 in the immune system in regulation of tumor control.…”

Section: Discussionmentioning

confidence: 99%

CD24 blunts oral squamous cancer development and dampens the functional expansion of myeloid-derived suppressor cells

et al. 2016

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CD24 expression has been implicated in the oncogenesis of multiple types of cancer and high tumor expression is considered a poor prognosis factor; however, the role of CD24 in oral cancer progression is unknown. Unlike other cancer types, we found that higher CD24 levels in human oral cancers are correlated to lower clinical stage and better overall survival. We then dissected the role of CD24 and mechanisms in oral cancer pathogenesis in mice using a genetic strategy and demonstrated that CD24 deficiency increased the oral cavity tumor burden in response to the carcinogen 4-nitroquioline 1-oxide (4-NQO). Immune profile analysis showed a significant expansion as well as increased suppressive function of myeloid-derived suppressor cells (MDSCs) in CD24 ¡/¡ mice, but no apparent impairment in T cells, B cells, or dendritic cells. Further, studies with an orthotopically transplanted syngeneic squamous carcinoma model in the tongue of CD24 ¡/¡ and CD24 C/¡ mice confirmed the protective roles of CD24 against cancer. Moreover, the difference in tumor growth between CD24 ¡/¡ and CD24 C/¡ mice was blunted by immunodepletion of MDSCs. We conclude that CD24 expression impedes MDSC expansion and function, and thus slows oral cancer oncogenesis. This study is the first to examine the role of CD24 in a de novo oral cancer model, and it highlights the need to consider the immune regulatory roles of CD24 in the development of CD24-targeted therapy for cancer.

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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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Identification of CD24 as a Cancer Stem Cell Marker in Human Nasopharyngeal Carcinoma

Cited by 50 publications

References 59 publications

β-Catenin is important for cancer stem cell generation and tumorigenic activity in nasopharyngeal carcinoma

β-Catenin is important for cancer stem cell generation and tumorigenic activity in nasopharyngeal carcinoma

CD24 blunts oral squamous cancer development and dampens the functional expansion of myeloid-derived suppressor cells

Spheres from cervical cancer cells display stemness and cancer drug resistance

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Identification of CD24 as a Cancer Stem Cell Marker in Human Nasopharyngeal Carcinoma

Cited by 50 publications

References 59 publications

&beta;-Catenin is important for cancer stem cell generation and tumorigenic activity in nasopharyngeal carcinoma

&beta;-Catenin is important for cancer stem cell generation and tumorigenic activity in nasopharyngeal carcinoma

CD24 blunts oral squamous cancer development and dampens the functional expansion of myeloid-derived suppressor cells

Spheres from cervical cancer cells display stemness and cancer drug resistance

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β-Catenin is important for cancer stem cell generation and tumorigenic activity in nasopharyngeal carcinoma

β-Catenin is important for cancer stem cell generation and tumorigenic activity in nasopharyngeal carcinoma