Shinichi Kimura1, Taishi Harada2, Kayo Ijichi3, Kentaro Tanaka1, Renpeng Liu1, Daisuke Shibahara1, Yuko Kawano1, Kohei Otsubo1, Yasuto Yoneshima1, Eiji Iwama1, Yoichi Nakanishi1, Isamu Okamoto1. 1. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 2. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Respiratory Medicine, Japan Community Healthcare Organization Kyushu Hospital, Kitakyushu, Japan. Electronic address: harada-t@kokyu.med.kyushu-u.ac.jp. 3. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Abstract
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.
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 SCLCpatients 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 SCLCpatients 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 SCLCpatients, and BDNF promoted the migration of TrkB-overexpressing SCLC cells. TrkB is thus a potential therapeutic target for SCLC.
Authors: Mohammad Malekan; Sasan Salehi Nezamabadi; Elham Samami; Mehdi Mohebalizadeh; Amene Saghazadeh; Nima Rezaei Journal: J Cancer Res Clin Oncol Date: 2022-09-29 Impact factor: 4.322
Authors: Vivian P Wagner; Manoela D Martins; Esra Amoura; Virgilio G Zanella; Rafael Roesler; Caroline B de Farias; Colin D Bingle; Pablo A Vargas; Lynne Bingle Journal: Biomedicines Date: 2020-11-24