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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.
AuthorsJózsef Dudás, Mario Bitsche, Volker Schartinger, Christina Falkeis, Georg Mathias Sprinzl, Herbert Riechelmann
JournalOral oncology (Oral Oncol) Vol. 47 Issue 2 Pg. 98-103 (Feb 2011) ISSN: 1879-0593 [Electronic] England
PMID21147546 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Elsevier Ltd. All rights reserved.
Chemical References
  • Brain-Derived Neurotrophic Factor
Topics
  • Animals
  • Blotting, Western
  • Brain-Derived Neurotrophic Factor (metabolism)
  • Carcinoma, Squamous Cell (genetics, metabolism, pathology)
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition (genetics, physiology)
  • Fibroblasts (metabolism, pathology, physiology)
  • Gene Expression Regulation, Neoplastic (genetics)
  • Humans
  • Mouth Neoplasms (genetics, metabolism, pathology)

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