Gunnar Wichmann1, Carolin Körner2, Andreas Boehm2, Christian Mozet2, Andreas Dietz2. 1. Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Leipzig, Germany gunnar.wichmann@medizin.uni-leipzig.de. 2. Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Leipzig, Germany.
Abstract
BACKGROUND: The outcome of patients with head and neck squamous cell carcinoma (HNSCC) is still poor. To improve therapy of HNSCC, biomarkers indicating progression of the disease or modifiers with potential as therapeutic targets and therapy need to be investigated. Since monocyte chemoattractant protein (MCP1) is potentially involved in tumorigenesis of HNSCC, we aimed to clarify its role in HNSCC and investigated the influence of stimulation by MCP1 and its depletion using antibodies against MCP1 (anti-MCP1) on colony formation by HNSCC cells. MATERIALS AND METHODS: Biopsies of HNSCC were treated according to the protocol of the FLAVINO assay with cisplatin, docetaxel, temsirolimus or cilengitide alone, or combined with MCP1 or anti-MCP1. After a 72-h incubation, ethanol-fixed and fluoresceine-isothiocyanate (FITC)-labeled epithelial colonies were counted. RESULTS: Colony formation was significantly suppressed by MCP1 and 3.3 μM cisplatin, while docetaxel, cilengitide and temsirolimus at concentrations of 0.275, 10 and 0.50 μM caused insignificant effects. Addition of MCP1 to cisplatin, docetaxel and cilengitide increased efficacy of cytostatics in inhibition of colony formation, whereas those with temsirolimus were increased by anti-MCP1 that when applied alone failed to modulate colony formation. Overall regarding facilitated chemosensitivity, there was a statistical trend in favor of MCP1 stimulation over depletion. CONCLUSION: Our ex vivo results show context-dependent effects of MCP1 in HNSCC cells. An increase of MCP1 level or its addition to cisplatin, docetaxel and cilengitide reduce colony formation but the efficacy of temsirolimus is augmented by MCP1 depletion. These context-dependently opposite outcomes call for further translational investigations in HNSCC. Copyright
BACKGROUND: The outcome of patients with head and neck squamous cell carcinoma (HNSCC) is still poor. To improve therapy of HNSCC, biomarkers indicating progression of the disease or modifiers with potential as therapeutic targets and therapy need to be investigated. Since monocyte chemoattractant protein (MCP1) is potentially involved in tumorigenesis of HNSCC, we aimed to clarify its role in HNSCC and investigated the influence of stimulation by MCP1 and its depletion using antibodies against MCP1 (anti-MCP1) on colony formation by HNSCC cells. MATERIALS AND METHODS: Biopsies of HNSCC were treated according to the protocol of the FLAVINO assay with cisplatin, docetaxel, temsirolimus or cilengitide alone, or combined with MCP1 or anti-MCP1. After a 72-h incubation, ethanol-fixed and fluoresceine-isothiocyanate (FITC)-labeled epithelial colonies were counted. RESULTS: Colony formation was significantly suppressed by MCP1 and 3.3 μM cisplatin, while docetaxel, cilengitide and temsirolimus at concentrations of 0.275, 10 and 0.50 μM caused insignificant effects. Addition of MCP1 to cisplatin, docetaxel and cilengitide increased efficacy of cytostatics in inhibition of colony formation, whereas those with temsirolimus were increased by anti-MCP1 that when applied alone failed to modulate colony formation. Overall regarding facilitated chemosensitivity, there was a statistical trend in favor of MCP1 stimulation over depletion. CONCLUSION: Our ex vivo results show context-dependent effects of MCP1 in HNSCC cells. An increase of MCP1 level or its addition to cisplatin, docetaxel and cilengitide reduce colony formation but the efficacy of temsirolimus is augmented by MCP1 depletion. These context-dependently opposite outcomes call for further translational investigations in HNSCC. Copyright
Authors: Hanadi Talal Ahmedah; Laurence H Patterson; Steven D Shnyder; Helen M Sheldrake Journal: Cancers (Basel) Date: 2017-05-26 Impact factor: 6.639
Authors: Amy J C Dohmen; Justin E Swartz; Michiel W M Van Den Brekel; Stefan M Willems; René Spijker; Jacques Neefjes; Charlotte L Zuur Journal: Cancers (Basel) Date: 2015-08-28 Impact factor: 6.639