Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer.
01 Mar 2009-Molecular Cancer Research (American Association for Cancer Research Inc.)-Vol. 7, Iss: 3, pp 330-338
TL;DR: Immunohistochemical analysis of 303 clinical specimens from three independent cohorts of lung cancer patients and controls show that expression of ALDH1 is positively correlated with the stage and grade of lung tumors and related to a poor prognosis for the patients with early-stage lung cancer.
Abstract: Tumor contains small population of cancer stem cells (CSC) that are responsible for its maintenance and relapse. Analysis of these CSCs may lead to effective prognostic and therapeutic strategies for the treatment of cancer patients. We report here the identification of CSCs from human lung cancer cells using Aldefluor assay followed by fluorescence-activated cell sorting analysis. Isolated cancer cells with relatively high aldehyde dehydrogenase 1 (ALDH1) activity display in vitro features of CSCs, including capacities for proliferation, self-renewal, and differentiation, resistance to chemotherapy, and expressing CSC surface marker CD133. In vivo experiments show that the ALDH1-positive cells could generate tumors that recapitulate the heterogeneity of the parental cancer cells. Immunohistochemical analysis of 303 clinical specimens from three independent cohorts of lung cancer patients and controls show that expression of ALDH1 is positively correlated with the stage and grade of lung tumors and related to a poor prognosis for the patients with early-stage lung cancer. ALDH1 is therefore a lung tumor stem cell-associated marker. These findings offer an important new tool for the study of lung CSCs and provide a potential prognostic factor and therapeutic target for treatment of the patients with lung cancer. (Mol Cancer Res 2009;7(3):330–8)
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Cites background from "Aldehyde dehydrogenase 1 is a tumor..."
...ALDH activity is a potential selective marker for cancer stem cells in many different types of cancer, such as breast cancer [53], bladder cancer [81], head and neck squamous cell carcinoma [82], lung cancer [83], and embryonal rhabdomyosarcoma [84]....
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TL;DR: ADCs can be modelled by KrasG12D expression (long latency), KrasD expression and Trp53-null, and epidermal growth factor receptor (EGFR)T790M/L858R, among other genetic models, and they are thought to arise from more distal airway cells.
Abstract: Nature Reviews Cancer 14, 535–546 (2014) In the original version of this article, the word 'proximal' was incorrectly used twice instead of 'distal' in two sentences in the legend for Figure 2. The sentences should have stated “ADCs can be modelled by KrasG12D expression (long latency), KrasG12D expression and Trp53-null, and epidermal growth factor receptor (EGFR)T790M/L858R, among other genetic models, and they are thought to arise from more distal airway cells.
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References
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TL;DR: The ability to prospectively identify tumorigenic cancer cells will facilitate the elucidation of pathways that regulate their growth and survival and strategies designed to target this population may lead to more effective therapies.
Abstract: Breast cancer is the most common malignancy in United States women, accounting for >40,000 deaths each year. These breast tumors are comprised of phenotypically diverse populations of breast cancer cells. Using a model in which human breast cancer cells were grown in immunocompromised mice, we found that only a minority of breast cancer cells had the ability to form new tumors. We were able to distinguish the tumorigenic (tumor initiating) from the nontumorigenic cancer cells based on cell surface marker expression. We prospectively identified and isolated the tumorigenic cells as CD44+CD24−/lowLineage− in eight of nine patients. As few as 100 cells with this phenotype were able to form tumors in mice, whereas tens of thousands of cells with alternate phenotypes failed to form tumors. The tumorigenic subpopulation could be serially passaged: each time cells within this population generated new tumors containing additional CD44+CD24−/lowLineage− tumorigenic cells as well as the phenotypically diverse mixed populations of nontumorigenic cells present in the initial tumor. The ability to prospectively identify tumorigenic cancer cells will facilitate the elucidation of pathways that regulate their growth and survival. Furthermore, because these cells drive tumor development, strategies designed to target this population may lead to more effective therapies.
10,058 citations
"Aldehyde dehydrogenase 1 is a tumor..." refers background in this paper
...Therefore, unlike the previously described CSC phenotype, which might require the use of a combination of several surface antigens (26), the Aldefluor-FACS would be a simple and effective approach for defining and isolating an enriched lung CSC population from cancer cell lines and could be potentially amenable to clinical applications....
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TL;DR: Stem cell biology has come of age: Unequivocal proof that stem cells exist in the haematopoietic system has given way to the prospective isolation of several tissue-specific stem and progenitor cells, the initial delineation of their properties and expressed genetic programmes, and the beginnings of their utility in regenerative medicine.
Abstract: Stem cell biology has come of age. Unequivocal proof that stem cells exist in the haematopoietic system has given way to the prospective isolation of several tissue-specific stem and progenitor cells, the initial delineation of their properties and expressed genetic programmes, and the beginnings of their utility in regenerative medicine. Perhaps the most important and useful property of stem cells is that of self-renewal. Through this property, striking parallels can be found between stem cells and cancer cells: tumours may often originate from the transformation of normal stem cells, similar signalling pathways may regulate self-renewal in stem cells and cancer cells, and cancer cells may include 'cancer stem cells' - rare cells with indefinite potential for self-renewal that drive tumorigenesis.
8,999 citations
"Aldehyde dehydrogenase 1 is a tumor..." refers background in this paper
...CSCs undergo selfrenewal, recapitulate the phenotype of the tumor from which they were derived, develop into phenotypically diverse cancer cell populations, proliferate extensively, and drive both continued expansion of malignant cells and resistance to chemotherapy (3, 4)....
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...(Mol Cancer Res 2009;7(3):330–8) Introduction Non-small cell lung cancer (NSCLC) is the most lethal of all cancers in the United States and worldwide mainly because of...
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...As a result, although conventional chemotherapeutic drugs can shrink lung tumors, their effects are usually transient, and they often do not appreciably extend the life of patients (1-8)....
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...Accumulating evidence has proposed a model in which tumorigenesis is driven by cancer stem cells (CSC) that are derived from mutated adult stem cells (3)....
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...The existence of lung CSCs could explain why current treatments for lung cancer cannot consistently eradicate tumor cells and ‘‘have reached a therapeutic plateau,’’ because these therapies target the bulk of cancer and are unlikely to eliminate CSCs (3, 4)....
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TL;DR: It is shown that normal and cancer human mammary epithelial cells with increased aldehyde dehydrogenase activity (ALDH) have stem/progenitor properties and these cells contain the subpopulation of normal breast epithelium with the broadest lineage differentiation potential and greatest growth capacity in a xenotransplant model.
3,766 citations
"Aldehyde dehydrogenase 1 is a tumor..." refers background or methods in this paper
...Murine and human hematopoietic and neural stem cells have high ALDH activity (10-15)....
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...score of the samples for ALDH1 was determined based on previously published criteria (15, 19)....
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...Increased ALDH1 activity has been found in stem cell populations in human multiple myeloma, acute myeloid leukemia, and brain and breast cancers (10-17)....
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TL;DR: Gaining a better insight into the mechanisms of stem-cell resistance to chemotherapy might lead to new therapeutic targets and better anticancer strategies.
Abstract: The contribution of tumorigenic stem cells to haematopoietic cancers has been established for some time, and cells possessing stem-cell properties have been described in several solid tumours. Although chemotherapy kills most cells in a tumour, it is believed to leave tumour stem cells behind, which might be an important mechanism of resistance. For example, the ATP-binding cassette (ABC) drug transporters have been shown to protect cancer stem cells from chemotherapeutic agents. Gaining a better insight into the mechanisms of stem-cell resistance to chemotherapy might therefore lead to new therapeutic targets and better anticancer strategies.
3,480 citations
"Aldehyde dehydrogenase 1 is a tumor..." refers background in this paper
...Third, according to the tumor stem cell theory, cancer can survive chemotherapy and relapse because of the resident CSCs that are drug resistant and can repopulate the tumor even when the bulk of nontumorigenic cells are killed (28-30)....
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TL;DR: Although bronchiolar cells and alveolar cells are proposed to be the precursor cells of adenocarcinoma, this work points to bronchioalveolar stem cells as the putative cells of origin for this subtype of lung cancer.
2,087 citations
"Aldehyde dehydrogenase 1 is a tumor..." refers background in this paper
...As is true in most human carcinogenesis, lung tumor growth and metastasis might be promoted by CSCs that are responsible for the aggressiveness of lung cancer (5-8)....
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..., Sca-1, a cell surface marker for bronchioalveolar stem cells in mice), there is no functional human homologue for them (8)....
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...As a result, although conventional chemotherapeutic drugs can shrink lung tumors, their effects are usually transient, and they often do not appreciably extend the life of patients (1-8)....
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