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.
Highlights
The neurotrophin and neurotrophin receptor signal path was initially identified in neural cells
In our recent study [20], we found that the conditioned medium of cultured fibroblasts in serum-deprived conditions support (i) cell proliferation, (ii) cell migration, and (iii) epithelial–mesenchymal transition (EMT) in tumor cells of head and neck squamous cell carcinoma (HNSCC)
Using RNA isolation, reverse transcription, PCR, and in situ hybridization, the mRNA expression of brain-derived neurotrophic factor (BDNF) and neurotrophin receptor tyrosine kinase-2 (NTRK2), and using immunohistochemistry, the protein synthesis of the NTRK2 gene product TrkB were investigated in normal mucosa from uvulopalatopharyngoplasties (UPPP)
Summary
The neurotrophin and neurotrophin receptor signal path was initially identified in neural cells. They were detected in some cancers in association with invasiveness [1]. The Trk family of receptors includes the neurotrophin receptor tyrosine kinase-2 (NTRK2) (TrkB) specific for brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) [5]. Both BDNF and TrkB are key factors in the development and maintenance of hearing function [6,7,8,9,10]. Brain-derived neurotrophic factor and its receptor moieties are instrumental to facilitate sensory neuronal survival in embryonic rat [11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
