Association of cancer metabolism-related proteins with oral carcinogenesis – indications for chemoprevention and metabolic sensitizing of oral squamous cell carcinoma?

Journal of Translational Medicine

Siegmar Reinert²  Wiebke Kraut²  Peter Teriete¹  Adelheid Munz²  Thorsten Biegner³  Max Lehmann²  Marcel Cetindis²  Martin Grimm² 

[1] Cancer Research Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA;Department of Oral and Maxillofacial Surgery, University Hospital Tuebingen, Osianderstrasse 2-8, Tuebingen 72076, Germany;Department of Pathology, University Hospital Tuebingen, Liebermeisterstrasse 8, Tuebingen 72076, Germany

关键词: Targeted anti-mitochondrial therapy;    Carbohydrate-restricted diets;    Mitochondrial oxidative phosphorylation;    Glycolysis-related proteins;    Tumor metabolism;    Oral squamous cell carcinoma;   

Others  :  1148681
DOI  :  10.1186/1479-5876-12-208

 received in 2014-05-05, accepted in 2014-07-02,  发布年份 2014

【 摘 要 】

Background

Tumor metabolism is a crucial factor for the carcinogenesis of oral squamous cell carcinoma (OSCC).

Methods

Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, PFK-1, LDHA, TKTL1), mitochondrial enzymes (SDHA, SDHB, ATP synthase) were analyzed in normal oral mucosa (n = 5), oral precursor lesions (simple hyperplasia, n = 11; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 42) by immunohistochemistry and real-time polymerase chain reaction (qPCR) analysis in OSCC cell lines. Metabolism-related proteins were correlated with proliferation activity (Ki-67) and apoptotic properties (TUNEL assay) in OSCC. Specificity of antibodies was confirmed by western blotting in cancer cell lines.

Results

Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, LDHA, TKTL1), and mitochondrial enzymes (SDHA, SDHB, ATP synthase) were significantly increased in the carcinogenesis of OSCC. Metabolic active regions of OSCC were strongly correlated with proliferating cancer (Ki-67+) cells without detection of apoptosis (TUNEL assay).

Conclusions

This study provides the first evidence of the expression of IGF-R1, glycolysis-related proteins GLUT-1, HK 2, PFK-1, LDHA, and TKTL1, as well as mitochondrial enzymes SDHA, SDHB, and ATP synthase in the multi-step carcinogenesis of OSCC. Both, hypoxia-related glucose metabolism and mitochondrial oxidative phosphorylation characteristics are associated with the carcinogenesis of OSCC. Acidosis and OXPHOS may drive a metabolic shift towards the pentose phosphate pathway (PPP). Therefore, inhibition of the PPP, glycolysis, and targeted anti-mitochondrial therapies (ROS generation) by natural compounds or synthetic vitamin derivatives may act as sensitizer for apoptosis in cancer cells mediated by adjuvant therapies in OSCC.

【 授权许可】

   
2014 Grimm et al.; licensee BioMed Central Ltd.

【 图 表 】

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