Objectives: TrkB is a receptor for brain-derived neurotrophic factor (BDNF) and is highly expressed in various cancers, with BDNF-TrkB signaling having been implicated in tumor progression and metastasis. The role of the BDNF-TrkB system in small cell lung cancer (SCLC), a neuroendocrine cancer, has remained unclear, however. We examined BDNF and TrkB expression in SCLC patients as well as the function of BDNF-TrkB signaling in SCLC cell lines.
Materials and methods: BDNF and TrkB expression in tumor specimens of 58 SCLC patients and 20 non-small cell lung cancer (NSCLC) patients was examined by immunohistochemistry and was scored on the basis of the distribution and intensity of staining. TrkB-overexpressing SCLC (SBC5TrkB) cells were established by retrovirus transduction and were examined for the effects of BDNF on intracellular signaling, cell proliferation, and cell migration in vitro.
Results: The staining score for TrkB in NSCLC and SCLC specimens was 2.80 ± 0.19 and 3.60 ± 0.15, respectively, whereas that for BDNF was 1.95 ± 0.32 and 2.76 ± 0.14, respectively. High levels of both TrkB and BDNF expression in SCLC tumors were significantly associated with poor overall survival in multivariate analysis (hazard ratio = 1.821, P = 0.036). BDNF activated AKT and ERK signaling pathways in and promoted the migration of SBC5TrkB cells, and these effects were attenuated by the pan-Trk inhibitor GNF-5837. GNF-5837 also inhibited the proliferation of SBC5TrkB cells in the presence of BDNF.
Conclusion: Coexpression of BDNF and TrkB was associated with poor prognosis in SCLC patients, and BDNF promoted the migration of TrkB-overexpressing SCLC cells. TrkB is thus a potential therapeutic target for SCLC.
Keywords: Brain-derived neurotrophic factor (BDNF); NTRK2 gene; Prognosis; Small cell lung cancer (SCLC); TrkB.
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