Aldehyde dehydrogenase: Its role as a cancer stem cell marker comes down to the specific isoform

Marcato, Paola; Dean, Cheryl A.; Giacomantonio, Carman A.; Lee, Patrick W.K.

doi:10.4161/cc.10.9.15486

Cited by 455 publications

(439 citation statements)

References 79 publications

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“…These vary depending on the cancer, and not all tumor cells identified by certain markers are cancer stemlike cells/tumor-initiating cells. 46 In this study, 18%, 10% and 9% of the upper urinary tract urothelial cell carcinoma cases had ALDH1 pos SOX2 neg , ALDH1 neg SOX2 pos and ALDH1 pos SOX2 pos tumor (Table 2). Furthermore, the number of upper urinary tract urothelial cell carcinoma cells immunohistochemically stained for both ALDH1 and SOX2, which are considered to have more characteristics of cancer stem-like cell/tumorinitiating cell, was limited in these cases (Supplementary Figure S2).…”

Section: Discussionmentioning

confidence: 52%

Prognostic impact of the expression of ALDH1 and SOX2 in urothelial cancer of the upper urinary tract

et al. 2013

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Aldehyde dehydrogenase 1 (ALDH1) and sex determining region-Y-related high mobility group box 2 (SOX2) have been identified as putative cancer stem-like cell/tumor-initiating cell markers in various cancer tissues. The aim of this study was to elucidate the prognostic impact of these putative cancer stem-like cell/tumorinitiating cell markers in upper urinary tract urothelial cell carcinoma. Immunohistochemical staining for ALDH1 and SOX2 was carried out on archival specimens from 125 patients with upper urinary tract urothelial cell carcinoma who underwent radical nephroureterectomy. The prognostic value of ALDH1 and SOX2 expression and other clinicopathological features was evaluated. On univariate analysis, tumor grade, pathological T stage, pathological N stage, lymphovascular invasion, ALDH1 expression and SOX2 expression were associated with a poor prognosis. On multivariate analysis, the independent factors of prognosis were tumor grade (P ¼ 0.014), pathological N stage (P ¼ 0.005) and ALDH1 expression (P ¼ 0.002). In subgroup analysis, those subgroups with no positive, one positive or two positive results in immunohistochemistry for ALDH1 and SOX2 expression had estimated 5-year cancer-specific survival rates of 80%, 49% and 22%, respectively (Po0.001). Neither ALDH1 nor SOX2 expression correlated with intravesical recurrence after radical nephroureterectomy. These findings suggest that cancer stem-like cells/tumor-initiating cells are linked to more aggressive behavior of upper urinary tract urothelial cell carcinoma, supporting the current cancer stem cell hypothesis. Thus, therapeutic targeting of cancer stem-like cells/tumor-initiating cells in upper urinary tract urothelial cell carcinoma is a future possibility.

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Section: Discussionmentioning

confidence: 52%

Prognostic impact of the expression of ALDH1 and SOX2 in urothelial cancer of the upper urinary tract

et al. 2013

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“…A subset of ALDH isoforms, most notably ALDH1A1, has been found to be upregulated in somatic and CSCs and may play roles in the detoxification of aldehydes, retinoic acid signalling and other cellular processes (Marcato et al 2011). A fluorescent substrate of ALDH, Aldefluor, allows the identification and purification of ALDH1-expressing cells (Storms et al 1999).…”

Section: Aldefluormentioning

confidence: 99%

“…Aldehyde dehydrogenase (ALDH) enzymes catalyse the oxidation of aldehydes into carboxylic acids and are encoded by 19 different isoforms in human (Marcato et al 2011). A subset of ALDH isoforms, most notably ALDH1A1, has been found to be upregulated in somatic and CSCs and may play roles in the detoxification of aldehydes, retinoic acid signalling and other cellular processes (Marcato et al 2011).…”

Section: Aldefluormentioning

confidence: 99%

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Epithelial ovarian cancer stem cells: underlying complexity of a simple paradigm

Garson¹,

Vanderhyden²

2015

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The lack of significant progress in the treatment of epithelial ovarian cancer (EOC) underscores the need to gain a better understanding of the processes that lead to chemoresistance and recurrence. The cancer stem cell (CSC) hypothesis offers an attractive explanation of how a subpopulation of cells within a patient's tumour might remain refractory to treatment and subsequently form the basis of recurrent chemoresistant disease. This review examines the literature defining somatic stem cells of the ovary and fallopian tube, two tissues that give rise to EOC. In addition, considerable research has been reviewed, that has identified subpopulations of EOC cells, based on marker expression (CD133, CD44, CD117, CD24, epithelial cell adhesion molecule, LY6A, ALDH1 and side population (SP)), which are enriched for tumour initiating cells (TICs). While many studies identified either CD133 or CD44 as markers useful for enriching for TICs, there is little consensus. This suggests that EOC cells may have a phenotypic plasticity that may preclude the identification of universal markers defining a CSC. The assay that forms the basis of quantifying TICs is the xenograft assay. Considerable controversy surrounds the xenograft assay and it is essential that some of the potential limitations be examined in this review. Highlighting such limitations or weaknesses is required to properly evaluate data and broaden our interpretation of potential mechanisms that might be contributing to the pathogenesis of ovarian cancer.

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“…30,68 Todaro et al showed that PTC, FTC and ATC contain a small population of tumourigenic cells with high ALDH activity and unlimited replication potential. Expanded indefinitely in vitro as tumour spheres, these ALDH high cells contain 25-60% of the clonogenic cells able to generate serial tumour xenografts.…”

Section: Thyroid Cancer Stem Cellsmentioning

confidence: 99%

Normal vs cancer thyroid stem cells: the road to transformation

et al. 2015

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Recent investigations in thyroid carcinogenesis have led to the isolation and characterisation of a subpopulation of stem-like cells, responsible for tumour initiation, progression and metastasis. Nevertheless, the cellular origin of thyroid cancer stem cells (SCs) remains unknown and it is still necessary to define the process and the target population that sustain malignant transformation of tissue-resident SCs or the reprogramming of a more differentiated cell. Here, we will critically discuss new insights into thyroid SCs as a potential source of cancer formation in light of the available information on the oncogenic role of genetic modifications that occur during thyroid cancer development. Understanding the fine mechanisms that regulate tumour transformation may provide new ground for clinical intervention in terms of prevention, diagnosis and therapy.Oncogene advance online publication, 11 May 2015; doi:10.1038/onc.2015.138

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Aldehyde dehydrogenase: Its role as a cancer stem cell marker comes down to the specific isoform

Cited by 455 publications

References 79 publications

Prognostic impact of the expression of ALDH1 and SOX2 in urothelial cancer of the upper urinary tract

Prognostic impact of the expression of ALDH1 and SOX2 in urothelial cancer of the upper urinary tract

Epithelial ovarian cancer stem cells: underlying complexity of a simple paradigm

Normal vs cancer thyroid stem cells: the road to transformation

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