Expression of brain-derived neurotrophic factor and its receptor TrkB is associated with poor prognosis and a malignant phenotype in small cell lung cancer

Shinichi Kimura, Taishi Harada, Kayo Ijichi, Kentaro Tanaka, Renpeng Liu, Daisuke Shibahara, Yuko Kawano, Kohei Otsubo, Yasuto Yoneshima, Eiji Iwama, Yoichi Nakanishi, Isamu Okamoto

研究成果: Contribution to journalArticle査読

12 被引用数 (Scopus)

抄録

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 (SBC5 TrkB ) 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 SBC5 TrkB cells, and these effects were attenuated by the pan-Trk inhibitor GNF-5837. GNF-5837 also inhibited the proliferation of SBC5 TrkB 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.

本文言語英語
ページ(範囲)98-107
ページ数10
ジャーナルLung Cancer
120
DOI
出版ステータス出版済み - 6 2018

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 呼吸器内科
  • 癌研究

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