Directly to content
  1. Publishing |
  2. Search |
  3. Browse |
  4. Recent items rss |
  5. Open Access |
  6. Jur. Issues |
  7. DeutschClear Cookie - decide language by browser settings

Glyoxalase 1 expression is associated with an unfavorable prognosis of oropharyngeal squamous cell carcinoma

Kreycy, Nele ; Gotzian, Christiane ; Fleming, Thomas ; Flechtenmacher, Christa ; Grabe, Niels ; Plinkert, Peter ; Hess, Jochen ; Zaoui, Karim

In: BMC Cancer, 17 (2017), Nr. 382. pp. 1-9. ISSN 1471-2407

[img]
Preview
PDF, English
Download (1MB) | Lizenz: Creative Commons LizenzvertragGlyoxalase 1 expression is associated with an unfavorable prognosis of oropharyngeal squamous cell carcinoma by Kreycy, Nele ; Gotzian, Christiane ; Fleming, Thomas ; Flechtenmacher, Christa ; Grabe, Niels ; Plinkert, Peter ; Hess, Jochen ; Zaoui, Karim underlies the terms of Creative Commons Attribution 3.0 Germany

Citation of documents: Please do not cite the URL that is displayed in your browser location input, instead use the DOI, URN or the persistent URL below, as we can guarantee their long-time accessibility.

Abstract

Background: Glyoxalase 1 is a key enzyme in the detoxification of reactive metabolites such as methylglyoxal and induced Glyoxalase 1 expression has been demonstrated for several human malignancies. However, the regulation and clinical relevance of Glyoxalase 1 in the context of head and neck squamous cell carcinoma has not been addressed so far. Methods: Argpyrimidine modification as a surrogate for methylglyoxal accumulation and Glyoxalase 1 expression in tumor cells was assessed by immunohistochemical staining of tissue microarrays with specimens from oropharyngeal squamous cell carcinoma patients (n = 154). Prognostic values of distinct Glyoxalase 1 staining patterns were demonstrated by Kaplan-Meier, univariate and multivariate Cox proportional hazard model analysis. The impact of exogenous methylglyoxal or a Glyoxalase 1 inhibitor on the viability of two established tumor cell lines was monitored by a colony-forming assay in vitro. Results: Glyoxalase 1 expression in tumor cells of oropharyngeal squamous cell carcinoma patients was positively correlated with the presence of Argpyrimidine modification and administration of exogenous methylglyoxal induced Glyoxalase 1 protein levels in FaDu and Cal27 cells in vitro. Cal27 cells with lower basal and methylglyoxal-induced Glyoxalase 1 expression were more sensitive to the cytotoxic effect at high methylgyoxal concentrations and both cell lines showed a decrease in colony formation with increasing amounts of a Glyoxalase 1 inhibitor. A high and nuclear Glyoxalase 1 staining was significantly correlated with shorter progression-free and disease-specific survival, and served as an independent risk factor for an unfavorable prognosis of oropharyngeal squamous cell carcinoma patients. Conclusions: Induced Glyoxalase 1 expression is a common feature in the pathogenesis of oropharyngeal squamous cell carcinoma and most likely represents an adaptive response to the accumulation of cytotoxic metabolites. Oropharyngeal squamous cell carcinoma patients with a high and nuclear Glyoxalase 1 staining pattern have a high risk for treatment failure, but might benefit from pharmacological targeting Glyoxalase 1 activity.

Item Type: Article
Journal or Publication Title: BMC Cancer
Volume: 17
Number: 382
Publisher: BioMed Central; Springer
Place of Publication: London; Berlin; Heidelberg
Date Deposited: 29 May 2017 09:25
Date: 2017
ISSN: 1471-2407
Page Range: pp. 1-9
Faculties / Institutes: Service facilities > Bioquant
Service facilities > German Cancer Research Center (DKFZ)
Medizinische Fakultät Heidelberg > Medizinische Universitäts-Klinik und Poliklinik
Medizinische Fakultät Heidelberg > HNO-Universitätsklinik
Medizinische Fakultät Heidelberg > Pathologisches Institut
Subjects: 610 Medical sciences Medicine
About | FAQ | Contact | Imprint |
OA-LogoDINI certificate 2013Logo der Open-Archives-Initiative