Isolation of primitive human hematopoietic progenitors on the basis of aldehyde dehydrogenase activity

Storms, Robert W.; Trujillo, Angelica; Springer, Judith; Shah, Lisa M.; Colvin, O. Michael; Ludeman, Susan M.; Smith, Clayton A.

doi:10.1073/pnas.96.16.9118

Cited by 483 publications

(433 citation statements)

References 38 publications

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“…Thus, ALDH1A1-expressing cells have a crucial role in the initiation and progression of esophageal squamous cell carcinoma. ALDH1A1 is a predominant isoform of aldehyde dehydrogenase family in mammals located in the cytoplasm 15,16 and is originally considered as a marker for normal hematopoietic progenitor cells, 17 and is also found in cancer cells with stem cell property, that is, cancer stem-like cells, in several malignant tumors including leukemia, 9 breast cancer 7 and lung cancer. 8,18 Wang et al 19 reported that ALDH1A1 was located in the nuclei of esophageal squamous cell carcinoma cells.…”

Section: Discussionmentioning

confidence: 99%

ALDH1A1 defines invasive cancer stem-like cells and predicts poor prognosis in patients with esophageal squamous cell carcinoma

et al. 2014

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Invasion and metastasis are the major cause of deaths in patients with esophageal cancer. In this study, we isolated cancer stem-like cells from an esophageal squamous cell carcinoma cell line EC109 based on aldehyde dehydrogenase 1A1 (ALDH1A1), and found that ALDH1A1 high cells possessed the capacities of self-renewal, differentiation and tumor initiation, indications of stem cell properties. To support their stemness, ALDH1A1 high cells exhibited increased potential of invasion and metastasis as compared with ALDH1A1 low cells. ALDH1A1 high esophageal squamous cell carcinoma cells expressed increased levels of mRNA for vimentin, matrix metalloproteinase 2, 7 and 9 (MMP2, MMP7 and MMP9), but decreased the level of E-cadherin mRNA, suggesting that epithelial-mesenchymal transition and secretary MMPs may be attributed to the high invasive and metastatic capabilities of ALDH1A1 high cells. Furthermore, we examined esophageal squamous cell carcinoma specimens from 165 patients and found that ALDH1A1 high cells were associated with esophageal squamous dysplasia and the grades, differentiation and invasion depth, lymph node metastasis and UICC stage of esophageal squamous cell carcinoma, as well as poor prognosis of patients. Our results provide the strong evidence that ALDH1A1 high cancer stem-like cells contribute to the invasion, metastasis and poor outcome of human esophageal squamous cell carcinoma. Modern Pathology (2014) 27, 775-783; doi:10.1038/modpathol.2013.189; published online 8 November 2013Keywords: aldehyde dehydrogenase 1A1; cancer stem-like cells; esophageal squamous carcinoma; invasion; metastasis; prognosis Esophageal squamous cell carcinoma is one of the most frequent fatal malignancies in the area from northern Iran to north-central China ('Asian esophageal cancer belt'). 1,2 The 5-year survival rate of esophageal squamous cell carcinoma patients after surgery and chemotherapy remains low owing to highly invasive and metastatic nature of esophageal squamous cell carcinoma. Cancer stem-like cells are a small subpopulation within tumors with the capacities for self-renewal and generating heterogeneous tumor cell lineages. 3 Recent studies suggest that cancer stem-like cells are responsible for invasion and metastasis of many tumor types. We have reported that cancer stem-like cells possess higher capability of invasion and metastasis in solid tumors. [4][5][6] However, the biomarkers related to invasion and metastasis of cancer stem-like cells

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Section: Discussionmentioning

confidence: 99%

ALDH1A1 defines invasive cancer stem-like cells and predicts poor prognosis in patients with esophageal squamous cell carcinoma

et al. 2014

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“…Such cells, called label-retaining cells [5,6], can now be purified out live in genetic models and used in functional assays [1]. Finally, stem cells can be enriched using the side population (SP) [7] and Aldefluor [8] assays, both of which take advantage of the preferential expression of detoxification molecules (e.g., ABC transporters such as ABCG2 in SP analysis) or enzymes (e.g., ALDH1A1 in Aldefluor assay) in adult stem cells. …”

Section: Heterogeneity Of Normal Stem/progenitor Cellsmentioning

confidence: 99%

Understanding cancer stem cell heterogeneity and plasticity

2012

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Heterogeneity is an omnipresent feature of mammalian cells in vitro and in vivo. It has been recently realized that even mouse and human embryonic stem cells under the best culture conditions are heterogeneous containing pluripotent as well as partially committed cells. Somatic stem cells in adult organs are also heterogeneous, containing many subpopulations of self-renewing cells with distinct regenerative capacity. The differentiated progeny of adult stem cells also retain significant developmental plasticity that can be induced by a wide variety of experimental approaches. Like normal stem cells, recent data suggest that cancer stem cells (CSCs) similarly display significant phenotypic and functional heterogeneity, and that the CSC progeny can manifest diverse plasticity. Here, I discuss CSC heterogeneity and plasticity in the context of tumor development and progression, and by comparing with normal stem cell development. Appreciation of cancer cell plasticity entails a revision to the earlier concept that only the tumorigenic subset in the tumor needs to be targeted. By understanding the interrelationship between CSCs and their differentiated progeny, we can hope to develop better therapeutic regimens that can prevent the emergence of tumor cell variants that are able to found a new tumor and distant metastases.

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“…The ALDEFLUOR (Stem Cell Technologies, Grenoble, France, http://www.stemcell.-com) technique has recently been developed to quantify ALDH activity level in viable cells [15,16]. Using ALDE-FLUOR BODIPY (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-5-proprionic acid)-aminoacetaldehyde (BAAA), a fluorescent synthetic substrate of ALDH, it is possible to isolate HSCs/HPCs using fluorescence-activated cell sorting (FACS) [17][18][19][20]. Similar to the SP phenotype, the ALDH activity level is considered as a stem cell marker because it is expressed in stem cells from several tissues, including hematopoietic, keratocytic, mesenchymal, neuronal, and endothelial stem cells [21,22].…”

Section: Introductionmentioning

confidence: 99%

Dual SP/ALDH Functionalities Refine the Human Hematopoietic Lin−CD34+CD38− Stem/Progenitor Cell Compartment

et al. 2009

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Identification of prevalent specific markers is crucial to stem/ progenitor cell purification. Determinants such as the surface antigens CD34 and CD38 are traditionally used to analyze and purify hematopoietic stem/progenitor cells (HSCs/HPCs). However, the variable expression of these membrane antigens poses some limitations to their use in HSC/HPC purification. Techniques based on drug/stain efflux through the ATP-binding cassette (ABC)G2 pump (side population [SP] phenotype) or on detection of aldehyde dehydrogenase (ALDH) activity have been independently developed and distinguish the SP and ALDH Bright (ALDH Br ) cell subsets for their phenotype and proliferative capability. In this study, we developed a multiparametric flow cytometric method associating both SP and ALDH activities on human lineage negative (Lin 2 ) bone marrow cells and sorted different cell fractions according to their SP/ALDH activity level. We find that Lin 2 CD34 1 CD38 Low/2 cells are found throughout the spectrum of ALDH expression and are enriched especially in ALDH Br cells when associated with SP functionality (SP/ALDH Br fraction). Furthermore, the SP marker identified G 0 cells in all ALDH fractions, allowing us to sort quiescent cells regardless of ALDH activity. Moreover, we show that, within the Lin 2 CD34 1 CD38 2 ALDH Br population, the SP marker identifies cells with higher primitive characteristics, in terms of stemness-related gene expression and in vitro and in vivo proliferative potential, than the Lin 2 CD34 1 CD38 2 ALDH Br main population cells. In conclusion, our study shows that the coexpression of SP and ALDH markers refines the Lin 2 CD34 1 CD38 2 hematopoietic compartment and identifies an SP/ALDH Br cell subset enriched in quiescent primitive HSCs/HPCs.

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Isolation of primitive human hematopoietic progenitors on the basis of aldehyde dehydrogenase activity

Abstract: ABSTRACT

Cited by 483 publications

References 38 publications

ALDH1A1 defines invasive cancer stem-like cells and predicts poor prognosis in patients with esophageal squamous cell carcinoma

ALDH1A1 defines invasive cancer stem-like cells and predicts poor prognosis in patients with esophageal squamous cell carcinoma

Understanding cancer stem cell heterogeneity and plasticity

Dual SP/ALDH Functionalities Refine the Human Hematopoietic Lin−CD34+CD38− Stem/Progenitor Cell Compartment

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