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A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma
Published on: January 5, 2017
Brain-Derived Neurotrophin and TrkB in Head and Neck Squamous Cell Carcinoma
József Dudás1, Anna Riml2, Raphaela Tuertscher3
1Department of Otorhinolaryngology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria. jozsef.dudas@i-med.ac.at.
Abstract:
We hypothesized that in head and neck squamous cell carcinoma (HNSCC), the neurotrophin brain-derived neurotrophic factor (BDNF) and its high affinity receptor TrkB regulate tumor cell survival, invasion, and therapy resistance. We used in situ hybridization for BDNF and immunohistochemistry (IHC) for TrkB in 131 HNSCC samples. Brain-derived neurotrophic factor was highly expressed in normal mucosa in HNSCC tissue and in cell lines, whereas only 42.74% of HNSCC tissue was TrkB⁺. One fourth of HNSCC cases was human papilloma virus (HPV)- positive, but the TrkB IHC frequency was not different in HPV-positive (HPV⁺) and negative cases. The UPCI-SCC090 cells expressed constitutive levels of TrkB. Transforming-growth-factor-β1 (1 ng/mL TGF-β1) induced TrkB in a subpopulation of SCC-25 cells. A single 10-µg/mL mitomycin C treatment in UPCI-SCC090 cells induced apoptosis and BDNF did not rescue them. The SCC-25 cells were resistant to the MMC treatment, and their growth decreased after TGF-β1 treatment, but was restored by BDNF if it followed TGF-β1. Taken together, BDNF might be ineffective in HPV⁺ HNSCC patients. In HPV- HNSCC patients, tumor cells did not die after chemotherapeutic challenge and BDNF with TGF-β1 could improve tumor cell survival and contribute to worse patient prognosis.
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