Single‐marker identification of head and neck squamous cell carcinoma cancer stem cells with aldehyde dehydrogenase

Clay, Matthew R.; Tabor, M.; Owen, Jennifer C.; Carey, Thomas E.; Bradford, Carol R.; Wolf, Gregory T.; Wicha, Max S.; Prince, Mark E.

doi:10.1002/hed.21315

Cited by 400 publications

(366 citation statements)

References 27 publications

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“…In a review performed by Januchowski et al, the association between high level expression of ALDH1A1 and poor prognosis was shown in breast (Black et al, 2009;Tanei et al, 2009), bladder and prostate cancer patients (Li et al, 2010). It has also been shown to be a marker of CSCs in many types of solid tumors, including liver (Lingala et al, 2010), head and neck (Clay et al, 2010), pancreas (Rasheed et al, 2010), lung (Rasheed et al, 2010) ovary (Deng et al, 2010), and colon carcinomas (Lugli et al, 2010). Similar results were reported by Tanei et al in another study on breast cancer indicating the association between high expression of ALDH1A1 with lower overall survival and increase the number of ALDH1A1+ cells after chemptherapy (Tanei et al, 2009), since chemotherapy cannot eradicate cancer stem cells (CSCs) expressing ALDH1A1.…”

Section: Discussionmentioning

confidence: 99%

ALDH1 in Combination with CD44 as Putative Cancer Stem Cell Markers are Correlated with Poor Prognosis in Urothelial Carcinoma of the Urinary Bladder

Keymoosi¹,

Gheytanchi²,

Asgari³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Section: Discussionmentioning

confidence: 99%

ALDH1 in Combination with CD44 as Putative Cancer Stem Cell Markers are Correlated with Poor Prognosis in Urothelial Carcinoma of the Urinary Bladder

Keymoosi¹,

Gheytanchi²,

Asgari³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…1 Recently, the EMT has been found to contribute to the progression and confer cancer cells with stem cell-like properties, in which the cells have a propensity for invasion, metastatic dissemination, resistance to certain therapy, persistence in tumours, and recurrence. 19,28 Understanding the molecular and cellular changes may generate novel targets that can overcome the aforementioned issues and reduce mortality. In this study, we made three novel observations that may help develop new treatments for OSCC: overexpression of Snail induced the SCC9 cells to undergo EMT; furthermore, these cells exhibited mesenchymal properties and were highly invasive, but not highly proliferative; and the induction of EMT conferred CSC-like properties to these mesenchymal cells.…”

Section: Discussionmentioning

confidence: 99%

Snail overexpression induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells

Zhu

Yang

et al. 2012

Laboratory Investigation

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Local invasiveness and distant metastasis are critical factors that contribute to oral squamous cell carcinoma-related deaths. Increasing evidence has shown that the epithelial to mesenchymal transition (EMT) is involved in cancer progression and is associated with the 'stemness' of cancer cells. Snail is a transcriptional factor that can induce EMT and preserve stem-cell function, which may induce resistance to radio-and chemotherapies in the cells. In the present study, SCC9 cells were transfected with an empty vector or a vector encoding human Snail (SCC9-S). Overexpression of Snail induced SCC9 cells to undergo EMT, in which the cells presented a fibroblast-like appearance, downregulated the epithelial markers E-cadherin and b-catenin, upregulated the mesenchymal marker vimentin, and associated with highly invasive and metastatic properties. Furthermore, the induction of EMT promoted cancer stem cell (CSC)-like characteristics in the SCC9-S cells, such as low proliferation, self-renewal, and CSC-like markers expression. These results indicate that overexpression of Snail induces EMT and promotes CSC-like traits in the SCC9 cells. Further understanding the role of Snail in cancer progression may reveal new targets for the prevention or therapy of oral cancers. Oral squamous cell carcinoma (OSCC) is the most frequent type of cancer in the oral cavity and is associated with high morbidity and poor prognosis. 1,2 Despite progress in surgery, chemotherapy, and radiotherapy, the 5-year survival rate has remained at 50-55% over the past several decades. 3 Local or regional recurrences and distant metastases have a critical role in this process, and the mechanism underlying their occurrence remains poorly understood. 2,4 During metastatic progression, tumour cells lose cell-cell adhesion, detach from the primary site, invade the basement membrane, survive and circulate in the blood vessels, leave the bloodstream, and finally colonise in a new host environment to form micrometastases. 2,5-7 A growing body of research strongly suggests that the epithelial to mesenchymal transition (EMT), which occurs normally during embryonic development, tissue remodelling, and wound healing, is a critical early event in tumour invasion and metastasis. [8][9][10] It is characterised by downregulation of epithelial markers, such as E-cadherin, and upregulation of mesenchymal markers, such as vimentin. During the process of EMT, epithelial cells acquire mesenchymal cell properties and show reduced intercellular adhesion and increased invasion. 11 The transcriptional repressor Snail, which is a zinc finger protein, first described in Drosophila melanogaster, can bind to the E-boxes in the human E-cadherin promoter and suppress its transcription. 12,13 Snail has previously been implicated in triggering EMT during embryonic development, fibrosis, and tumour progression. 14 This process also occurs in the progression of carcinomas (including oral carcinoma cells), following the downregulation of E-cadherin expression or co-expression of NB...

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“…ALDH1, a detoxifying enzyme responsible for the oxidation of intracellular aldehydes, is also considered to be a common marker for both normal stem cells and malignant CSCs from HNSCC (10,24,25). Overexpression of both CD44v3 and ALDH1 appears to be closely associated with CSC-mediated HNSCC development and progression (10).…”

Section: Isolation Of a Highly Tumorigenic Cell Population From Tumormentioning

confidence: 99%

Up-regulation of Histone Methyltransferase, DOT1L, by Matrix Hyaluronan Promotes MicroRNA-10 Expression Leading to Tumor Cell Invasion and Chemoresistance in Cancer Stem Cells from Head and Neck Squamous Cell Carcinoma

Bourguignon

Wong

Shiina

2016

Journal of Biological Chemistry

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Human head and neck squamous cell carcinoma is a solid tumor malignancy associated with major morbidity and mortality. In this study, we determined that human head and neck squamous cell carcinoma-derived HSC-3 cells contain a subpopulation of cancer stem cells (CSCs) characterized by a high level of CD44v3 and aldehyde dehydrogenase-1 (ALDH1) expression. Importantly, matrix hyaluronan (HA) induces the up-regulation of stem cell markers that display the hallmark CSC properties. Histone methyltransferase, DOT1L, is also upregulated by HA in CSCs (isolated from HSC-3 cells). Further analyses indicate that the stimulation of microRNA-10b (miR10b) expression is DOT1L-specific and HA/CD44-dependent in CSCs. This process subsequently results in the overexpression of RhoGTPases and survival proteins leading to tumor cell invasion and cisplatin resistance. Treatment of CSCs with DOT1L-specific small interfering RNAs (siRNAs) effectively blocks HA/CD44-mediated expression of DOT1L, miR-10b production, and RhoGTPase/survival protein up-regulation as well as reduces tumor cell invasion and enhances chemosensitivity. CSCs were also transfected with a specific anti-miR-10b inhibitor to silence miR-10b expression and block its target functions. Our results demonstrate that the anti-miR-10 inhibitor not only decreases RhoGTPase/survival protein expression and tumor cell invasion, but also increases chemosensitivity in HA-treated CSCs. Taken together, these findings strongly support the contention that histone methyltransferase, DOT1L-associated epigenetic changes induced by HA play pivotal roles in miR-10 production leading to upregulation of RhoGTPase and survival proteins. All of these events are critically important for the acquisition of cancer stem cell properties, including self-renewal, tumor cell invasion, and chemotherapy resistance in HA/CD44-activated head and neck cancer.Human head and neck squamous cell carcinoma (HNSCC) 2 is a highly malignant cancer associated with major morbidity and mortality (1). A number of studies have identified specific molecules expressed in HNSCC that correlate with tumor behavior. Among such molecules are matrix hyaluronan (HA) (2, 3) and its cell surface receptor, CD44 (4). HA is a major component of the ECM and is significantly enriched in many types of tumors (5). CD44 is a multifunctional transmembrane glycoprotein expressed in HNSCC cells and carcinoma tissues (6, 7). It is commonly expressed as various isoforms generated by alternative mRNA splicing of variant exons inserted into an extracellular membrane-proximal site (8). Most importantly, expression of certain CD44 variant (CD44v) isoforms (especially, CD44v3) is known to be associated with HNSCC progression (6, 9, 10).HNSCC appears to contain a subpopulation of cancer stem cells (CSCs) characterized by a high level of CD44v3 expression (10). In fact, CD44v3 is thought to be one of the important cell surface markers for CSCs (10). These isolated CSCs are capable of generating phenotypically distinct cells resulting in heteroge...

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Single‐marker identification of head and neck squamous cell carcinoma cancer stem cells with aldehyde dehydrogenase

Cited by 400 publications

References 27 publications

ALDH1 in Combination with CD44 as Putative Cancer Stem Cell Markers are Correlated with Poor Prognosis in Urothelial Carcinoma of the Urinary Bladder

ALDH1 in Combination with CD44 as Putative Cancer Stem Cell Markers are Correlated with Poor Prognosis in Urothelial Carcinoma of the Urinary Bladder

Snail overexpression induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells

Up-regulation of Histone Methyltransferase, DOT1L, by Matrix Hyaluronan Promotes MicroRNA-10 Expression Leading to Tumor Cell Invasion and Chemoresistance in Cancer Stem Cells from Head and Neck Squamous Cell Carcinoma

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