Li Zhu1, Jochen A Werner, Robert Mandic. 1. Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Giessen and Marburg, Campus Marburg, Marburg, Germany.
Abstract
BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) represent the most common malignancies of the upper aerodigestive tract. Expression of tropomyosin-related kinase B (TrkB) was found to be essential to prevent anoikis in rat intestinal epithelial cells allowing for survival of cells outside the epithelial cell layer and subsequent metastatic spread. The aim of the present study was to examine the potential role of TrkB in HNSCC disease. MATERIALS AND METHODS: SDS-PAGE and Western blot analysis of TrkB expression were performed under standard conditions. Immunohistochemistry was performed with the Avidin Biotin Complex method, whereas immunocytochemistry was performed by fluorescence staining. Tumor cell invasiveness was measured by an in vitro invasion assay. RESULTS: A variable but consistent expression of TrkB could be observed in HNSCC tissues and cell lines, whereas no significant expression was seen in the healthy control tissue (soft palate). Immunohisto- and cytochemical staining further demonstrated pronounced TrkB expression in HNSCC tumor cells. However, the invasive properties of TrkB-expressing HNSCC cells were not significantly altered after treatment with 10 or 100 ng/ml brain-derived neurotrophic factor, the natural ligand of TrkB. CONCLUSION: The presented data implicates to a great extent that TrkB plays a significant role in HNSCC disease since it was consistently found to be overexpressed in cells of this tumor entity. We conclude that the role of this receptor tyrosine kinase is rather the prevention of anoikis, as demonstrated earlier, and less the modulation of HNSCC invasiveness, since invasion was not affected after receptor stimulation. Further studies should investigate possible inhibitors of TrkB and their suitability for the treatment of head and neck cancer.
BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) represent the most common malignancies of the upper aerodigestive tract. Expression of tropomyosin-related kinase B (TrkB) was found to be essential to prevent anoikis in rat intestinal epithelial cells allowing for survival of cells outside the epithelial cell layer and subsequent metastatic spread. The aim of the present study was to examine the potential role of TrkB in HNSCC disease. MATERIALS AND METHODS:SDS-PAGE and Western blot analysis of TrkB expression were performed under standard conditions. Immunohistochemistry was performed with the Avidin Biotin Complex method, whereas immunocytochemistry was performed by fluorescence staining. Tumor cell invasiveness was measured by an in vitro invasion assay. RESULTS: A variable but consistent expression of TrkB could be observed in HNSCC tissues and cell lines, whereas no significant expression was seen in the healthy control tissue (soft palate). Immunohisto- and cytochemical staining further demonstrated pronounced TrkB expression in HNSCC tumor cells. However, the invasive properties of TrkB-expressing HNSCC cells were not significantly altered after treatment with 10 or 100 ng/ml brain-derived neurotrophic factor, the natural ligand of TrkB. CONCLUSION: The presented data implicates to a great extent that TrkB plays a significant role in HNSCC disease since it was consistently found to be overexpressed in cells of this tumor entity. We conclude that the role of this receptor tyrosine kinase is rather the prevention of anoikis, as demonstrated earlier, and less the modulation of HNSCC invasiveness, since invasion was not affected after receptor stimulation. Further studies should investigate possible inhibitors of TrkB and their suitability for the treatment of head and neck cancer.
Authors: József Dudás; Mario Bitsche; Volker Schartinger; Christina Falkeis; Georg Mathias Sprinzl; Herbert Riechelmann Journal: Oral Oncol Date: 2010-12-13 Impact factor: 5.337