Sebastian Blatt1, Nadine Voelxen2, Keyvan Sagheb3, Andreas Max Pabst3,4, Stefan Walenta2, Thies Schroeder5, Wolfgang Mueller-Klieser2, Thomas Ziebart3. 1. Department of Oral and Maxillofacial Surgery, University Medical Center of the Johannes Gutenberg-University of Mainz, 55131, Mainz, Germany. sebastian.blatt@gmx.de. 2. Institute of Pathophysiology, University Medical Center of the Johannes Gutenberg-University of Mainz, 55128, Mainz, Germany. 3. Department of Oral and Maxillofacial Surgery, University Medical Center of the Johannes Gutenberg-University of Mainz, 55131, Mainz, Germany. 4. Department of Oral and Maxillofacial Surgery, Federal Armed Forces Hospital Koblenz, Rübenacherstr. 170, 56072, Koblenz, Germany. 5. Department of Physical Chemistry, Johannes Gutenberg-University of Mainz, 55128, Mainz, Germany.
Abstract
OBJECTIVES: Lactate as a key regulator of the glycolytic phenotype has been recently described in fueling tumor growth and metastatic spread in head and neck squamous cell carcinoma (HNSCC). However, in context of tumor recurrence following adjuvant radiation, the underlying mechanisms remain uncertain. We therefore investigate the role of lactate towards radioresistance in HNSCC in this prospective study for the first time in vivo. MATERIALS AND METHODS: Herein, we analyzed biopsies of primary squamous cell carcinoma after surgery and adjuvant irradiation in 17 patients. Tumor tissue levels of ATP, glucose, and lactate were detected using induced metabolic bioluminescence imaging (imBI) and correlated with clinical data within an observation period of up to 15 years. RESULTS: High amounts of lactate levels in tumors of HNSCC are significantly negatively correlated with overall patient survival. Moreover, high expression of lactate in a primary tumor site is significantly correlated with tumor recurrence post radiation, whereas ATP and/or glucose showed no such correlation. CONCLUSION: Lactate can be seen not only as a waste product of altered glycolytic metabolism but also as a key master of malignancy as well as resistance mechanism towards irradiation. CLINICAL RELEVANCE: High expression of lactate levels in tumor tissue, obtained by metabolic bioluminescence imaging, may therefore serve as a predictor for overall and recurrence-free survival and could represent a future biomarker in the validation of adjuvant irradiation.
OBJECTIVES:Lactate as a key regulator of the glycolytic phenotype has been recently described in fueling tumor growth and metastatic spread in head and neck squamous cell carcinoma (HNSCC). However, in context of tumor recurrence following adjuvant radiation, the underlying mechanisms remain uncertain. We therefore investigate the role of lactate towards radioresistance in HNSCC in this prospective study for the first time in vivo. MATERIALS AND METHODS: Herein, we analyzed biopsies of primary squamous cell carcinoma after surgery and adjuvant irradiation in 17 patients. Tumor tissue levels of ATP, glucose, and lactate were detected using induced metabolic bioluminescence imaging (imBI) and correlated with clinical data within an observation period of up to 15 years. RESULTS: High amounts of lactate levels in tumors of HNSCC are significantly negatively correlated with overall patient survival. Moreover, high expression of lactate in a primary tumor site is significantly correlated with tumor recurrence post radiation, whereas ATP and/or glucose showed no such correlation. CONCLUSION:Lactate can be seen not only as a waste product of altered glycolytic metabolism but also as a key master of malignancy as well as resistance mechanism towards irradiation. CLINICAL RELEVANCE: High expression of lactate levels in tumor tissue, obtained by metabolic bioluminescence imaging, may therefore serve as a predictor for overall and recurrence-free survival and could represent a future biomarker in the validation of adjuvant irradiation.
Entities:
Keywords:
Head and neck squamous cell carcinoma (HNSCC); Induced metabolic bioluminescence imaging (imBI); Patient survival; Radioresistance; Tumor metabolism
Authors: Thomas Ziebart; Stefan Walenta; Martin Kunkel; Torsten E Reichert; Wilfried Wagner; Wolfgang Mueller-Klieser Journal: J Cancer Res Clin Oncol Date: 2010-04-11 Impact factor: 4.553
Authors: Iris L Romero; Abir Mukherjee; Hilary A Kenny; Lacey M Litchfield; Ernst Lengyel Journal: Clin Cancer Res Date: 2015-02-15 Impact factor: 12.531
Authors: David A Mankoff; Janet F Eary; Jeanne M Link; Mark Muzi; Joseph G Rajendran; Alexander M Spence; Kenneth A Krohn Journal: Clin Cancer Res Date: 2007-06-15 Impact factor: 12.531
Authors: Becky M Bola; Amy L Chadwick; Filippos Michopoulos; Kathryn G Blount; Brian A Telfer; Kaye J Williams; Paul D Smith; Susan E Critchlow; Ian J Stratford Journal: Mol Cancer Ther Date: 2014-10-03 Impact factor: 6.261
Authors: Nadine Fabienne Voelxen; Sebastian Blatt; Pascal Knopf; Maurice Henkel; Christina Appelhans; Leonardo A R Righesso; Andreas Pabst; Jutta Goldschmitt; Stefan Walenta; Andreas Neff; Wolfgang Mueller-Klieser; Thomas Ziebart Journal: Clin Oral Investig Date: 2017-07-22 Impact factor: 3.573
Authors: Gregor Brandstetter; Sebastian Blatt; Jutta Goldschmitt; Louise Taylor; Paul Heymann; Bilal Al-Nawas; Thomas Ziebart Journal: Clin Oral Investig Date: 2020-06-03 Impact factor: 3.573
Authors: Susana Romero-Garcia; María Maximina B Moreno-Altamirano; Heriberto Prado-Garcia; Francisco Javier Sánchez-García Journal: Front Immunol Date: 2016-02-16 Impact factor: 7.561
Authors: Le Tang; Fang Wei; Yingfen Wu; Yi He; Lei Shi; Fang Xiong; Zhaojian Gong; Can Guo; Xiayu Li; Hao Deng; Ke Cao; Ming Zhou; Bo Xiang; Xiaoling Li; Yong Li; Guiyuan Li; Wei Xiong; Zhaoyang Zeng Journal: J Exp Clin Cancer Res Date: 2018-04-23