CD44 as a stem cell marker in head and neck squamous cell carcinoma

Faber, Anne; Barth, Christine; Hörmann, K.; Kassner, Stefan; Schultz, Johannes; Sommer, Ulrich; Stern‐Straeter, Jens; Thorn, Carsten; Goessler, Ulrich Reinhart

doi:10.3892/or.2011.1322

Cited by 38 publications

(40 citation statements)

References 12 publications

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“…The transcription factors SOX2 and Oct3/4 are essential for maintaining the self-renewal capacity and pluripotency of embryonic and adult SCs. CD133 + cells in OSCC form holoclones and possess self-renewal capacity (51), and CD44 + cells in HNSCC possess the capacity for self-renewal and differentiation (52). However, the usefulness of CD44 as a marker of CSCs in OSCC is questionable as CD44 is expressed by normal oral epithelial cells (53,54).…”

Section: Concept and Identification Of Cscsmentioning

confidence: 94%

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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Section: Concept and Identification Of Cscsmentioning

confidence: 94%

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

Ren

Zhang

2016

Oncology Letters

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“…34), and a highly hypoxic tumor microenvironment contributes to an increased clonogenic potential (20,35). CD44 is a widely explored CSC marker in HNSCC (30,36,37). A study by de Jong and colleagues showed that CD44 and CD44 protein levels significantly predict local recurrence after radiotherapy in patients with early-stage laryngeal cancers (38).…”

Section: Discussionmentioning

confidence: 99%

Low Cancer Stem Cell Marker Expression and Low Hypoxia Identify Good Prognosis Subgroups in HPV(−) HNSCC after Postoperative Radiochemotherapy: A Multicenter Study of the DKTK-ROG

Linge

Löck

Gudziol

et al. 2016

Clinical Cancer Research

113

143

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Purpose: To investigate the impact of hypoxia-induced gene expression and cancer stem cell (CSC) marker expression on outcome of postoperative cisplatin-based radiochemotherapy (PORT-C) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).Experimental Design: Expression of the CSC markers CD44, MET, and SLC3A2, and hypoxia gene signatures were analyzed in the resected primary tumors using RT-PCR and nanoString technology in a multicenter retrospective cohort of 195 patients. CD44 protein expression was further analyzed in tissue microarrays. Primary endpoint was locoregional tumor control.Results: Univariate analysis showed that hypoxia-induced gene expression was significantly associated with a high risk of locoregional recurrence using the 15-gene signature (P ¼ 0.010) or the 26-gene signature (P ¼ 0.002). In multivariate analyses, in patients with HPV16 DNA-negative but not with HPV16 DNA-positive tumors the effect of hypoxia-induced genes on locoregional control was apparent (15-gene signature: HR 4.54, P ¼ 0.006; 26-gene signature: HR 10.27, P ¼ 0.024). Furthermore, MET, SLC3A2, CD44, and CD44 protein showed an association with locoregional tumor control in multivariate analyses (MET: HR 3.71, P ¼ 0.016; SLC3A2: HR 8.54, P ¼ 0.037; CD44: HR 3.36, P ¼ 0.054; CD44 protein n/a because of no event in the CD44-negative group) in the HPV16 DNA-negative subgroup.Conclusions: We have shown for the first time that high hypoxia-induced gene expression and high CSC marker expression levels correlate with tumor recurrence after PORT-C in patients with HPV16 DNA-negative HNSCC. After validation in a currently ongoing prospective trial, these parameters may help to further stratify patients for individualized treatment de-escalation or intensification strategies.

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“…Many researchers have reported that high expression of these markers indicates bad clinical features and poor prognosis (Lee et al 2009;Wang et al 2012;Ni et al 2013). The CSC hypothesis also has been connected to pharyngolaryngeal cancer (Faber et al 2011;Janisiewicz et al 2012), and CD44 was one of the most reported CSC markers.…”

Section: Introductionmentioning

confidence: 99%

CD44 Expression Is Predictive of Poor Prognosis in Pharyngolaryngeal Cancer: Systematic Review and Meta-Analysis

Chai

Liu

Wang

et al. 2014

Tohoku J. Exp. Med.

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Pharyngolaryngeal cancer is one of the most common head and neck cancer worldwide, and the early diagnosis and prognosis prediction are still difficult because of lacking in reliable cell markers. Although the expression of CD44 has been reported to correlate with poor prognosis of pharyngolaryngeal cancer in most literatures, some controversies still exist. Since the limited patient numbers within independent studies, here we performed a meta-analysis to clarify the correlations between CD44 expression and clinicopathological features and prognosis in pharyngolaryngeal cancer. A search of PubMed, ISI Web of Science and China National Knowledge Infrastructure databases (up to June 2013) was performed. Nineteen studies with 1,405 patients met the inclusion criteria. The expression of pan-CD44, including all variant isoforms, was detected in 58.0% (14.1-79.2%) specimens, while CD44-v6 (variant isoform 6 of CD44) was expressed in 54.8% (12-79.2%). In pooled analysis, CD44 expression was significantly associated with larger tumor size (T category, RR (relative risk) = 1.21, 95% CI: 1.01-1.46), lymph nodes metastasis (N category, RR = 1.94, 95% CI: 1.38-2.73) and poor prognosis [3-year overall survival (OS): RR = 0.70, 95% CI: 0.53-0.91; 5-year OS: RR = 0.66, 95% CI: 0.66-0.94]. In the stratified analysis of CD44 isoforms, high expression of CD44-v6 was related with a poor 5-year OS rate (RR = 0.53, 95% CI: 0.37-077). We propose that CD44 expression is associated with tumor size, lymph node metastasis, and poor prognosis in pharyngolaryngeal cancer patients.

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CD44 as a stem cell marker in head and neck squamous cell carcinoma

Cited by 38 publications

References 12 publications

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

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

Low Cancer Stem Cell Marker Expression and Low Hypoxia Identify Good Prognosis Subgroups in HPV(−) HNSCC after Postoperative Radiochemotherapy: A Multicenter Study of the DKTK-ROG

CD44 Expression Is Predictive of Poor Prognosis in Pharyngolaryngeal Cancer: Systematic Review and Meta-Analysis

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