CD44: A Cancer Stem Cell–Related Biomarker with Predictive Potential for Radiotherapy

Baumann, Michaël; Krause, Mechthild

doi:10.1158/1078-0432.ccr-10-2244

Cited by 78 publications

(54 citation statements)

References 10 publications

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“…In contrast to the hypoxia profiles, CSC marker expression correlated in our study not only with locoregional control but also with distant metastases. Expression of CSC markers has been suggested as a potential surrogate of CSC density, that is, of the number of cells at risk to metastasize per given volume of tumor tissue (30,34,36,46,48,49). Further mechanistic investigations into the relationship of hypoxia, stemness, and metastatic risk in HNSCC, in correlation with clinical data, appears therefore to be an interesting avenue for better stratification of patients for systemic therapies and for discovery of novel targets.…”

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

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117

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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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

Self Cite

117

143

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“…Prince et al first demonstrated that CD44 expression could be used to isolate a subpopulation with increased tumorigenicity in head and neck tumors (Prince et al, 2007). Several independent studies also confirm that CD44 either alone or in combination has the properties of a cancer stem cell marker and being a tumor initiator (Baumann et al, 2010;Chikamatsu et al, 2012). Certain forms of CD44 (i.e.,v3,v6,v10) are associated with tumor progression and metastatic spread of HNSCC .…”

Section: Methods Of Identification Of Cancer Stem Cellsmentioning

confidence: 99%

Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma: A Review

Satpute

Hazarey²,

Ahmed³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Research indicates that a small population of cancer cells is highly tumorigenic, endowed with the capacity for self-renewal, and has the ability to differentiate into cells that constitute the bulk of tumors. These cells are considered the ''drivers'' of the tumorigenic process in some tumor types, and have been named cancer stem cells (CSC). Epithelial-mesenchymal transition (EMT) appears to be involved in the process leading to the acquisition of stemness by epithelial tumor cells. Through this process, cells acquire an invasive phenotype that may contribute to tumor recurrence and metastasis. CSC have been identified in human head and neck squamous cell carcinomas (HNSCC) using markers such as CD133 and CD44 expression, and aldehyde dehydrogenase (ALDH) activity. Head and neck cancer stem cells reside primarily in perivascular niches in the invasive fronts where endothelial-cell initiated events contribute to their survival and function. Clinically, CSC enrichment has been shown to be enhanced in recurrent disease, treatment failure and metastasis. CSC represent a novel target of study given their slow growth and innate mechanisms conferring treatment resistance. Further understanding of their unique phenotype may reveal potential molecular targets to improve therapeutic and survival outcomes in patients with HNSCC. Here, we discuss the state-of-the-knowledge on the pathobiology of cancer stem cells, with a focus on the impact of these cells on head and neck tumor progression, metastasis and recurrence due to treatment failure.

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“…72,73 Similar results have been reported for experimental studies in animal models using fractionated radiation treatment 74 and the expression of the stem-cell-related marker CD44 has been reported to correlate with local control in early laryngeal cancers treated with radiation. 75 Interestingly, in the studies of West et al 76 discussed above, the plating efficiency (PE) of the cells from cervical cancers was not found to be as good a predictor of patient outcome as the SF2 value determined in vitro. However, in vitro assays may not reflect well the long-term potential for proliferation required of CSCs.…”

Section: Cancer Stem Cellsmentioning

confidence: 97%