In vitro and in vivo expression of aldehyde dehydrogenase 1 in oral squamous cell carcinoma

Ota, Nobutaka; Ohno, Jun; Seno, Kei; Taniguchi, Koki; Ozeki, Satoru

doi:10.3892/ijo.2013.2188

Cited by 25 publications

(21 citation statements)

References 28 publications

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“…The histochemical activity of ALDH1 is known to be one of the functional markers for mesenchymal stem cells (MSC) [16,17]. We applied the Aldefluor assay [18,19] to the frozen sections containing the bone defects. Cells positive for ALDH1 activity tended to accumulate in a scattered pattern within the replaced fibrous connective tissue (Fig 4A).…”

Section: Resultsmentioning

confidence: 99%

Salmon DNA Accelerates Bone Regeneration by Inducing Osteoblast Migration

et al. 2017

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The initial step of bone regeneration requires the migration of osteogenic cells to defective sites. Our previous studies suggest that a salmon DNA-based scaffold can promote the bone regeneration of calvarial defects in rats. We speculate that the salmon DNA may possess osteoinductive properties, including the homing of migrating osteogenic cells. In the present study, we investigated the influence of the salmon DNA on osteoblastic differentiation and induction of osteoblast migration using MG63 cells (human preosteoblasts) in vitro. Moreover, we analyzed the bone regeneration of a critical-sized in vivo calvarial bone defect (CSD) model in rats. The salmon DNA enhanced both mRNA and protein expression of the osteogenesis-related factors, runt-related transcription factor 2 (Runx2), alkaline phosphatase, and osterix (OSX) in the MG63 cells, compared with the cultivation using osteogenic induction medium alone. From the histochemical and immunohistochemical assays using frozen sections of the bone defects from animals that were implanted with DNA disks, many cells were found to express aldehyde dehydrogenase 1, one of the markers for mesenchymal stem cells. In addition, OSX was observed in the replaced connective tissue of the bone defects. These findings indicate that the DNA induced the migration and accumulation of osteogenic cells to the regenerative tissue. Furthermore, an in vitro transwell migration assay showed that the addition of DNA enhanced an induction of osteoblast migration, compared with the medium alone. The implantation of the DNA disks promoted bone regeneration in the CSD of rats, compared with that of collagen disks. These results indicate that the salmon DNA enhanced osteoblastic differentiation and induction of migration, resulting in the facilitation of bone regeneration.

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Section: Resultsmentioning

confidence: 99%

Salmon DNA Accelerates Bone Regeneration by Inducing Osteoblast Migration

et al. 2017

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“…Ectopic Orai1 expression markedly increases ALDH1+ cell population in the non-tumorigenic oral epithelial cells. ALDH1 has been found to be a marker for stem cells in different types of cancer, including OSCC [50, 51]. ALDH1+ cancer cells displayed higher self-renewal, migration, and tumorigenic potential than ALDH1- cells [50, 52, 53].…”

Section: Discussionmentioning

confidence: 99%

Orai1 promotes tumor progression by enhancing cancer stemness via NFAT signaling in oral/oropharyngeal squamous cell carcinoma

Lee¹,

Rigas²,

Lee³

et al. 2016

Oncotarget

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Emerging evidence indicates that Orai1, a key calcium channel for store-operated Ca2+ entry, is associated with human cancer. However, the underlying mechanism by which Orai1 regulates cancer progression remains unknown. Here we report that intracellular level of Orai1 is increased in a stepwise manner during oral/oropharyngeal carcinogenesis and highly expressed in cancer stem-like cell (CSC)-enriched populations of human oral/oropharyngeal squamous cell carcinoma (OSCC). Ectopic Orai1 expression converted non-tumorigenic immortalized oral epithelial cells to malignant cells that showed CSC properties, e.g., self-renewal capacity, increased ALDH1HIGH cell population, increased key stemness transcription factors, and enhanced mobility. Conversely, inhibition of Orai1 suppressed tumorigenicity and CSC phenotype of OSCC, indicating that Orai1 could be an important element for tumorigenicity and stemness of OSCC. Mechanistically, Orai1 activates its major downstream effector molecule, NFATc3. Knockdown of NFATc3 in the Orai1-overexpressing oral epithelial cells abrogates the effect of Orai1 on CSC phenotype. Moreover, antagonist of NFAT signaling also decreases CSC phenotype, implying the functional importance of Orai1/NFAT axis in OSCC CSC regulation. Our study identifies Orai1 as a novel molecular determinant for OSCC progression by enhancing cancer stemness, suggesting that inhibition of Orai1 signaling may offer an effective therapeutic modality against OSCC.

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“…26 However, Ota et al found no correlation between overexpression of ALDH1 and lower overall survival or relapse-free survival, but did find a correlation with local recurrence in vivo. 27 Cisplatin-surviving cells have exhibited high protein expression of ALDH1 and ATP-binding cassette, a high invasive capacity, and the ability to self-renew. These features confer the ability to initiate and drive primary tumour growth, invasion, metastasis, resistance to chemotherapy, 27 and local recurrence.…”

Section: Discussionmentioning

confidence: 99%

“…27 Cisplatin-surviving cells have exhibited high protein expression of ALDH1 and ATP-binding cassette, a high invasive capacity, and the ability to self-renew. These features confer the ability to initiate and drive primary tumour growth, invasion, metastasis, resistance to chemotherapy, 27 and local recurrence. 13 Head and neck SCCs that express little or no ALDH1A1 may be more responsive to chemotherapy due to the deficiency in the metabolism of retinaldehyde into retinoic acid.…”

Section: Discussionmentioning

confidence: 99%

Protein expression of CYP1A1, CYP1B1, ALDH1A1, and ALDH2 in young patients with oral squamous cell carcinoma

Kaminagakura

Caris

Coutinho‐Camillo

et al. 2016

International Journal of Oral and Maxillofacial Surgery

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The purpose of this study was to evaluate the expression of the enzymes involved in the biotransformation of tobacco and alcohol. A study group of 41 young patients (≤40 years old) with oral squamous cell carcinoma (OSCC) was compared to 59 control subjects (≥50 years old) with tumours of similar clinical stages and topographies. The immunohistochemical expression of CYP1A1, CYP1B1, ALDH1A1, and ALDH2 was evaluated using the tissue microarray technique. There was a predominance of males, smokers, and alcohol drinkers in both groups. Most tumours were located in the tongue (43.9% vs. 50.8%), were well-differentiated (63.4% vs. 56.6%), and were in clinical stages III or IV (80.5% vs. 78.0%). No difference was observed in the expression of CYP1A1, ALDH1A1, or ALDH2 between the two groups. CYP1A1 and ALDH2 protein expression had no influence on the prognosis. The immunoexpression of CYP1B1 was significantly higher in the control group than in the young group (P<0.001). The 5-year relapse-free survival was better in patients with CYP1B1 overexpression vs. protein underexpression (64% vs. 25%; P<0.05), regardless of age. ALDH1A1 expression improved relapse-free survival in young patients. These results suggest a lower risk of recurrence with increased metabolism of carcinogens by CYP1B1. Further studies involving other genes and proteins are necessary to complement the results of this research.

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In vitro and in vivo expression of aldehyde dehydrogenase 1 in oral squamous cell carcinoma

Cited by 25 publications

References 28 publications

Salmon DNA Accelerates Bone Regeneration by Inducing Osteoblast Migration

Salmon DNA Accelerates Bone Regeneration by Inducing Osteoblast Migration

Orai1 promotes tumor progression by enhancing cancer stemness via NFAT signaling in oral/oropharyngeal squamous cell carcinoma

Protein expression of CYP1A1, CYP1B1, ALDH1A1, and ALDH2 in young patients with oral squamous cell carcinoma

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