The Evolving Concepts of Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma

Shah, Amit; Patel, Shilpa; Pathak, Jigna; Swain, Niharika; Kumar, Shria

doi:10.1155/2014/842491

Cited by 28 publications

(22 citation statements)

References 65 publications

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“…CS L Cs contribute to tumor progression and recurrence in multiple cancer types, including OSCCs [15, 16, 19, 17, 18, 20–22]. Previous studies with normal tissue-specific stem cells suggest that the AHR contributed to properties of “stem-ness” [36, 37, 42, 43].…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies with normal tissue-specific stem cells suggest that the AHR contributed to properties of “stem-ness” [36, 37, 42, 43]. One readily assessed marker of stem-ness is elevated expression of ALDH1, an enzyme implicated in chemoresistance [44] the activity of which can be quantified via flow cytometry [16, 20]. In contrast to other tumor types, expression of surface CS L C markers, such as CD44 and CD24, is highly variable and not reliable in OSCC [16, 20, 22].…”

Section: Resultsmentioning

confidence: 99%

“…One readily assessed marker of stem-ness is elevated expression of ALDH1, an enzyme implicated in chemoresistance [44] the activity of which can be quantified via flow cytometry [16, 20]. In contrast to other tumor types, expression of surface CS L C markers, such as CD44 and CD24, is highly variable and not reliable in OSCC [16, 20, 22]. Therefore, a fluorescence-based ALDH1 enzyme activity assay [44] was used to quantify ALDH1 activity in HSC-3 and CAL27 cells in the absence or presence of diverse AHR ligands and/or AHR inhibitors.…”

Section: Resultsmentioning

confidence: 99%

“…CS L Cs are defined as a relatively small subset of chemotherapy- and radiotherapy-resistant, invasive, metastatic tumor cells that are highly efficient at tumor initiation [19–22]. Oral CS L Cs also tend to exhibit higher levels of ALDH1, an enzyme associated with chemo- and radio-resistance, than non-CS L Cs [16, 20]. Indeed, there is a direct correlation between ALDH levels and disease stage, prognosis, and chemotherapeutic resistance [18, 21].…”

Section: Introductionmentioning

confidence: 99%

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Role for the Aryl Hydrocarbon Receptor and Diverse Ligands in Oral Squamous Cell Carcinoma Migration and Tumorigenesis

Stanford

Ramirez-Cardenas

Wang

et al. 2016

Molecular Cancer Research

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Over 45,000 new cases of oral and pharyngeal cancers are diagnosed and account for over 8,000 deaths a year in the United States. An environmental chemical receptor, the aryl hydrocarbon receptor (AHR), has previously been implicated in oral squamous cell carcinoma (OSCC) initiation as well as in normal tissue-specific stem cell self-renewal. These previous studies inspired the hypothesis that the AHR plays a role in both the acquisition and progression of OSCC, as well as in the formation and maintenance of cancer stem-like cells. To test this hypothesis, AHR activity in two oral squamous cell lines was modulated with AHR prototypic, environmental and bacterial AHR ligands, AHR-specific inhibitors, and phenotypic, genomic and functional characteristics were evaluated. The data demonstrate that: 1) primary OSCC tissue expresses elevated levels of nuclear AHR as compared to normal tissue, 2) Ahr mRNA expression is up-regulated in 320 primary OSCC, 3) AHR hyper-activation with several ligands, including environmental and bacterial ligands, significantly increases AHR activity, ALDH1 activity, and accelerates cell migration, 4) AHR inhibition blocks the rapid migration of OSCC cells and reduces cell chemoresistance, 5) AHR knockdown inhibits tumorsphere formation in low adherence conditions, and 6) AHR knockdown inhibits tumor growth and increases overall survival in vivo. These data demonstrate that the AHR plays an important role in development and progression of OSCC, and specifically cancer stem-like cells. Prototypic, environmental and bacterial AHR ligands may exacerbate OSCC by enhancing expression of these properties. Implications This study, for the first time, demonstrates the ability of diverse AHR ligands to regulate AHR activity in oral squamous cell carcinoma cells, as well as regulate several important characteristics of oral cancer stem cells, in vivo and in vitro.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Role for the Aryl Hydrocarbon Receptor and Diverse Ligands in Oral Squamous Cell Carcinoma Migration and Tumorigenesis

Stanford

Ramirez-Cardenas

Wang

et al. 2016

Molecular Cancer Research

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show abstract

“…CSCs represent a small subpopulation of tumor cells that express a number of stem cell markers [7,8]. CSCs have the unique ability to self-renew and form differentiated progeny, which results in tumors composed of a heterogeneous cell population [6,9]. Tumor cells that undergo epithelial to mesenchymal transition represent a key population of cells that lead to formation of metastases [10].…”

Section: Introductionmentioning

confidence: 99%

Dysregulated signaling pathways in Human Papilloma Virus positive oropharyngeal cancers

Linga¹,

Moskovitz²,

Ganguly³

et al. 2016

J Stem Cell Res Med

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These authors contributed equally to this work. AbstractSmoking and infection with Human Papilloma virus (HPV) are important risk factors in head and neck squamous cell carcinoma (HNSCC). In spite of the fact that HPV-associated HNSCC patients tend to respond better to current treatment strategies than non-HPV associated HNSCC, some patients with HPVassociated HNSCC develop disease recurrences and develop distant metastases, which can be resistant to current treatment strategies. Cancer stem cells (CSCs) are believed to underlie the development of this resistant phenotype. In this study we examined the expression of CSC markers genes, as well as that of the STAT3 and Notch pathway genes in HPV-associated HNSCC patients, which we previously found to be overexpressed in glioma CSCs. Xenografts were established in immunocompromised mice from two patients (UTSCC-1 and UTSCC-2) with HPV-associated HNSCC that differed in their history of tobacco use. RNA extracted from both tumors showed high expression of SOX2, Nestin, CD133 and CD44, but the UTSCC-2 tumor from a patient with a history of heavy tobacco use showed significantly overexpressed SOX2, CD44 and CD133 compared to UTSCC-1. Moreover, UTSCC-2 significantly overexpressed many Notch pathway genes. Immunochemistry of STAT3 and pSTAT3 also showed strong expression of STAT3 and pSTAT3 in UTSCC-2 tumor. Serial transplantation of UTSCC-1 enhanced tumor formation, resulted in lung metastasis, and overexpression of STAT3 and NOTCH pathway genes. In conclusion, genes implicated in CSCs, STAT3 and NOTCH pathways are overexpressed in HPV-associated HNSCC, suggesting that these pathways may serve as novel targets for therapeutic intervention for this subset of patients.

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Surface Markers for the Identification of Cancer Stem Cells

Pronoy,

Islam,

Gopalan

et al. 2024

Methods in Molecular Biology

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The Evolving Concepts of Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma

Cited by 28 publications

References 65 publications

Role for the Aryl Hydrocarbon Receptor and Diverse Ligands in Oral Squamous Cell Carcinoma Migration and Tumorigenesis

Role for the Aryl Hydrocarbon Receptor and Diverse Ligands in Oral Squamous Cell Carcinoma Migration and Tumorigenesis

Dysregulated signaling pathways in Human Papilloma Virus positive oropharyngeal cancers

Surface Markers for the Identification of Cancer Stem Cells

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