title: Fibroblasts produce brain-derived neurotrophic factor and induce mesenchymal transition of oral tumor cells.
abstract: Fibroblasts (Fibs) contribution to neoplastic progression, tumor growth, angiogenesis, and metastasis has been recently reported by several research groups. In this study it was investigated if fibroblasts are the source of brain-derived neurotrophic factor (BDNF), which plays a crucial role in the progression of oral squamous cell carcinoma. In a novel in vitro system oral Fibs were cultured with SCC-25 lingual squamous cell carcinoma cells for 7days. Factors related with this interaction were investigated by quantitative PCR and western blot. In the co-culture, fibroblasts were converted to carcinoma-associated fibroblasts (CAFs), which in return initiated epithelial-mesenchymal transition (EMT) of SCC-25 cells. The induced CAFs produced increased levels of BDNF, which interacted with the increased-expressed neurothrophin receptor B (TrkB) on EMT-converted SCC-25 cells. Possible regulatory factors of BDNF expression (tumor necrosis factor-α and interleukin-1-β) were detected both in CAFs and EMT-tumor cells. In CAFs: IL-1β-, in SCC-25 cells TNF-α-gene-expression was significantly increased in co-culture conditions. Activated fibroblasts (CAFs) and mesenchymal transitioned tumor cells might use the BDNF-TrkB axis and its regulation to harmonize their interaction in the process of tumor progression.
authors.affiliation: Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria. Jozsef.Dudas@i-med.ac.at
authors.forename: József
authors.initials: J
authors.lastname: Dudás
authors.forename: Mario
authors.initials: M
authors.lastname: Bitsche
authors.forename: Volker
authors.initials: V
authors.lastname: Schartinger
authors.forename: Christina
authors.initials: C
authors.lastname: Falkeis
authors.forename: Georg Mathias
authors.initials: GM
authors.lastname: Sprinzl
authors.forename: Herbert
authors.initials: H
authors.lastname: Riechelmann
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D019208:Brain-Derived Neurotrophic Factor