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

Fibroblasts produce brain-derived neurotrophic factor and induce mesenchymal transition of oral tumor cells.
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DOI:
10.1016/j.oraloncology.2010.11.002
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发表时间:
2011-02
期刊:
影响因子:
4.8
通讯作者:
Riechelmann, Herbert
Riechelmann, Herbert
中科院分区:
医学2区
文献类型:
--
作者:
Dudas, Jozsef;Bitsche, Mario;Schartinger, Volker;Falkeis, Christina;Sprinzl, Georg Mathias;Riechelmann, Herbert

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成纤维细胞(Fibs)对肿瘤进展、肿瘤生长、血管生成和转移的贡献最近已被几个研究小组报道。在这项研究中,它被调查,如果成纤维细胞的来源脑源性神经营养因子(BDNF),这在口腔鳞状细胞癌的进展中起着至关重要的作用。在一个新的体外系统中,口腔纤维与SCC-25舌鳞状细胞癌细胞一起培养7天。通过定量PCR和western blot方法研究了这种相互作用的相关因素。在共培养中,成纤维细胞转化为癌相关成纤维细胞(CAF),反过来启动SCC-25细胞的上皮-间质转化(EMT)。诱导CAFs产生的BDNF水平增加,与EMT转化的SCC-25细胞上表达增加的神经营养素受体B(Trk B)相互作用。在CAFs和EMT-肿瘤细胞中均检测到BDNF表达的可能调控因子(肿瘤坏死因子-α和白细胞介素-1-β)。在CAFs中,IL-1β-,SCC-25细胞中TNF-α-基因表达在共培养条件下显著增加。活化的成纤维细胞(CAFs)和间充质转化的肿瘤细胞可能利用BDNF-TrkB轴及其调节来协调它们在肿瘤进展过程中的相互作用。
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.
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