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Aldehyde dehydrogenase activity is a cancer stem cell marker of tongue squamous cell carcinoma.

ABSTRACT: Accumulating data reveal that aldehyde dehydrogenase (ALDH) activity is a cancer stem cell marker in several types of human cancers. Whether ALDH also defines cancer stem cells of tongue squamous cell carcinoma is unknown. In the present study, we performed the Aldefluor assay to detect ALDH enzymatic activity, and used flow cytometry to isolate ALDH+ and ALDH- cells based on their ALDH activity in the Tca8113 tongue squamous cell carcinoma cell line. We found that Tca8113 cells harbored 1.3% of ALDH+ cells, which exhibited higher proliferation capacity than their ALDH- counterparts and parental cells. Sorted ALDH+ cells were able to differentiate and generate ALDH- cells in vitro. Moreover, in serum-free medium, ALDH+, but not ALDH- cells, survived and formed tumorspheres. The suppression subtractive hybridization assay revealed 68 overexpressed or underexpressed genes in the ALDH+ subpopulation relative to ALDH- cells, which included a set of known cancer stem cell-related genes. Thus, our data demonstrated that a small subset of Tca8113 cells with high ALDH enzymatic activity display characteristics of cancer stem cells, suggesting that ALDH activity may be a cancer stem cell marker for tongue squamous cell carcinoma.

SUBMITTER: Zou B

PROVIDER: S-EPMC3493091 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Aldehyde dehydrogenase activity is a cancer stem cell marker of tongue squamous cell carcinoma.

Zou Bo B Sun Shoujuan S Qi Xiaojuan X Ji Ping P

Molecular medicine reports 20120203 4

Accumulating data reveal that aldehyde dehydrogenase (ALDH) activity is a cancer stem cell marker in several types of human cancers. Whether ALDH also defines cancer stem cells of tongue squamous cell carcinoma is unknown. In the present study, we performed the Aldefluor assay to detect ALDH enzymatic activity, and used flow cytometry to isolate ALDH+ and ALDH- cells based on their ALDH activity in the Tca8113 tongue squamous cell carcinoma cell line. We found that Tca8113 cells harbored 1.3% of ...[more]

PMID: 22307065

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Project description:Background: Previous investigations have demonstrated the role of Aldehyde Dehydrogenase 2 (ALDH2) levels in the cancer initiation and progression, prognosis, and treatment response in kinds of malignancies. However, its significance in the head and neck squamous cell carcinoma (HNSC) by different human papillomavirus (HPV) statuses remains unclear. Methods: We conducted an in-depth analysis of ALDH2 in HNSC using various bioinformatics tools, investigating its expression, alteration, differential levels, prognostic significance, molecular interactions, immune characteristics, and conducting experimental validation through immunohistochemistry (IHC) arrays and Western blot to compare expression levels between tumor and normal tissues, analyze the associations with clinicopathological features, and investigate its responses to chemotherapies. Results: ALDH2 levels are downregulated in HNSC tissues and associated with higher American Joint Committee on Cancer (AJCC) T classification and worse overall survival in HPV-unrelated HNSC, yet not in HPV-related HNSC. ALDH2 is positively regulated by copy-number variation and negatively regulated by DNA methylation. The association of ALDH2 with prognosis may be due to its interaction with ALDH6A1, and its co-expressed genes are predictive biomarkers of HNSC. We also found high ALDH2 levels in bulk tumors are associated with increased immune surveillance cells, such as naïve B cells and M1 macrophages in HPV-unrelated HNSC. IHC and western blot showed that ALDH2 is downregulated in the oral cavity, hypopharyngeal cancers, and well-differentiated carcinoma. In vitro, low ALDH2 levels showed reduced response to 5-fluorouracil in HNSC-derived cell lines. Conclusion: Our analyses revealed the genetic and cellular targets and drug response of ALDH2 in HNSC. We also found ALDH2 is involved in regulating the immune response of the tumor microenvironment, and high levels of ALDH2 in bulk HNSC may enhance antitumor immunity, which could improve prognosis. These findings suggest that ALDH2 could be a potential biomarker in improving risk stratification and tailoring treatment strategies in HNSC patients, especially in the HPV-unrelated subgroup.

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Aldehyde dehydrogenase activity is a cancer stem cell marker of tongue squamous cell carcinoma.

Publications

Aldehyde dehydrogenase activity is a cancer stem cell marker of tongue squamous cell carcinoma.

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