Development of a new therapeutic strategy for large cell neuroendocrine carcinoma targeting TrkB/BDNF signaling pathway

大细胞神经内分泌癌（LCNEC）标本中原肌球蛋白相关激酶B （TrkB）和脑源性神经营养因子（BDNF）的表达明显高于其他组织学类型。此外，切除标本中TrkB和BDNF的高表达与晚期、术后复发和较差的总生存率显著相关。在体外实验中，TrkB/BDNF信号通过MMP-2和MMP-9的表达参与了侵袭性。此外，TrkB/BDNF信号通路参与了锚定非依赖性生长和肿瘤发生。这些结果表明TrkB/BDNF信号可能是LCNEC的潜在治疗靶点和预后因素。

There were significantly higher Tropomyosin-related kinase B (TrkB) and Brain-derived neurotrophic factor (BDNF) expressions in large cell neuroendocrine carcinoma (LCNEC) specimen than those in any other histological types. Furthermore higher expressions of TrkB and BDNF in resected specimen significantly correlated with advanced stage, postoperative recurrence, and poor overall survival. In vitro experiment, TrkB/BDNF signaling contributed to the invasiveness through MMP-2 and MMP-9 expressions. In addition, TrkB/BDNF signaling was involved in anchor-independent growth and tumorigenesis. These results suggest that TrkB/BDNF signaling may be a potential therapeutic target and a prognostic factor for LCNEC.