Fibroblasts produce brain-derived neurotrophic factor and induce mesenchymal transition of oral tumor cells

• Published in: Oral oncology Vol. 47; no. 2; pp. 98 - 103
• Main Authors: Dudás, József, Bitsche, Mario, Schartinger, Volker, Falkeis, Christina, Sprinzl, Georg Mathias, Riechelmann, Herbert
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.02.2011; Elsevier
• Subjects: Animals; Biological and medical sciences; Blotting, Western; Brain-Derived Neurotrophic Factor - metabolism; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell Line, Tumor; Co-culture insert; Epithelial-Mesenchymal Transition - genetics; Epithelial-Mesenchymal Transition - physiology; Fibroblasts - metabolism; Fibroblasts - pathology; Fibroblasts - physiology; Gene Expression Regulation, Neoplastic - genetics; Hematology, Oncology and Palliative Medicine; HNSCC; Humans; Medical sciences; Metastasis; Mouth Neoplasms - genetics; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; Neurotrophin; Oral cancer; Otolaryngology; Otorhinolaryngology. Stomatology; SDF; Tumor progression; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Neurotrophin; SDF; Co-culture insert; Oral cancer; HNSCC; Tumor progression; Metastasis; Stomatology; ENT; Malignant tumor; Cancerology; Oral cavity disease; Brain derived neurotrophic factor; Fibroblast; Tumor cell; Culture; Cancer
• ISSN: 1368-8375; 1879-0593
• DOI: 10.1016/j.oraloncology.2010.11.002

Summary 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 7 days. 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.