TrkB/BDNF signaling pathway is a potential therapeutic target for pulmonary large cell neuroendocrine carcinoma

Seiichi Odate, Katsuya Nakamura, Hideya Ohnishi, Masayuki Kojima, Akihiko Uchiyama, kenji nakano, Masato Kato, Masao Tanaka, Mitsuo Katano

研究成果: ジャーナルへの寄稿記事

33 引用 (Scopus)

抄録

Tropomyosin-related kinase B (TrkB) plays an important role in tumor progression in various kinds of cancers; however, little is known about biological significance of TrkB in human lung cancer, especially large cell neuroendocrine carcinoma (LCNEC). We hereby investigated the expressions of TrkB and its ligand brain-derived neurotrophic factor (BDNF) in clinical specimens and their influences on phenotypes of invasiveness and tumorigenicity for LCNEC. The expressions of TrkB and BDNF analyzed by immunohistochemistry for patients samples with lung cancer (n=104) were significantly higher in neuroendocrine tumor (NET) compared with non-NET. In particular, LCNEC, a subtype of NET, exhibited significantly higher TrkB and BDNF expressions than another NET type: small cell lung cancer (SCLC), and a significant correlation between TrkB and BDNF expressions was noted in LCNEC but not in SCLC. In vitro assay, exogenous BDNF addition enhanced the invasion into matrigels of LCNEC cells, whereas inhibition of TrkB or BDNF suppressed matrix metalloproteinase-2 and -9 activities and the invasiveness. Exogenous BDNF also increased anchor-independent colony formation on soft agar gels for LCNEC, while inhibition of TrkB or BDNF suppressed the anchorage-independency. In vivo experiments, implanted LCNEC cells pretreated with TrkB-siRNA developed no subcutaneous tumor in all six nude mice, although those with control-siRNA formed tumors in four of six nude mice. In conclusion, BDNF/TrkB signal is involved in malignant progression of invasiveness and tumorigenicity for LCNEC, and may be a potential target for LCNEC without standard therapy.

元の言語英語
ページ(範囲)205-214
ページ数10
ジャーナルLung Cancer
79
発行部数3
DOI
出版物ステータス出版済み - 3 1 2013

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Neuroendocrine Carcinoma
Large Cell Carcinoma
Brain-Derived Neurotrophic Factor
Lung
Neuroendocrine Tumors
Neuroendocrine Cells
Therapeutics
Small Cell Lung Carcinoma
Neoplasms
Nude Mice
Small Interfering RNA
Lung Neoplasms
tropomyosin kinase
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Agar
Gels
Immunohistochemistry
Ligands
Phenotype

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

これを引用

TrkB/BDNF signaling pathway is a potential therapeutic target for pulmonary large cell neuroendocrine carcinoma. / Odate, Seiichi; Nakamura, Katsuya; Ohnishi, Hideya; Kojima, Masayuki; Uchiyama, Akihiko; nakano, kenji; Kato, Masato; Tanaka, Masao; Katano, Mitsuo.

:: Lung Cancer, 巻 79, 番号 3, 01.03.2013, p. 205-214.

研究成果: ジャーナルへの寄稿記事

Odate, S, Nakamura, K, Ohnishi, H, Kojima, M, Uchiyama, A, nakano, K, Kato, M, Tanaka, M & Katano, M 2013, 'TrkB/BDNF signaling pathway is a potential therapeutic target for pulmonary large cell neuroendocrine carcinoma', Lung Cancer, 巻. 79, 番号 3, pp. 205-214. https://doi.org/10.1016/j.lungcan.2012.12.004
Odate, Seiichi ; Nakamura, Katsuya ; Ohnishi, Hideya ; Kojima, Masayuki ; Uchiyama, Akihiko ; nakano, kenji ; Kato, Masato ; Tanaka, Masao ; Katano, Mitsuo. / TrkB/BDNF signaling pathway is a potential therapeutic target for pulmonary large cell neuroendocrine carcinoma. :: Lung Cancer. 2013 ; 巻 79, 番号 3. pp. 205-214.
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AU - Odate, Seiichi

AU - Nakamura, Katsuya

AU - Ohnishi, Hideya

AU - Kojima, Masayuki

AU - Uchiyama, Akihiko

AU - nakano, kenji

AU - Kato, Masato

AU - Tanaka, Masao

AU - Katano, Mitsuo

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N2 - Tropomyosin-related kinase B (TrkB) plays an important role in tumor progression in various kinds of cancers; however, little is known about biological significance of TrkB in human lung cancer, especially large cell neuroendocrine carcinoma (LCNEC). We hereby investigated the expressions of TrkB and its ligand brain-derived neurotrophic factor (BDNF) in clinical specimens and their influences on phenotypes of invasiveness and tumorigenicity for LCNEC. The expressions of TrkB and BDNF analyzed by immunohistochemistry for patients samples with lung cancer (n=104) were significantly higher in neuroendocrine tumor (NET) compared with non-NET. In particular, LCNEC, a subtype of NET, exhibited significantly higher TrkB and BDNF expressions than another NET type: small cell lung cancer (SCLC), and a significant correlation between TrkB and BDNF expressions was noted in LCNEC but not in SCLC. In vitro assay, exogenous BDNF addition enhanced the invasion into matrigels of LCNEC cells, whereas inhibition of TrkB or BDNF suppressed matrix metalloproteinase-2 and -9 activities and the invasiveness. Exogenous BDNF also increased anchor-independent colony formation on soft agar gels for LCNEC, while inhibition of TrkB or BDNF suppressed the anchorage-independency. In vivo experiments, implanted LCNEC cells pretreated with TrkB-siRNA developed no subcutaneous tumor in all six nude mice, although those with control-siRNA formed tumors in four of six nude mice. In conclusion, BDNF/TrkB signal is involved in malignant progression of invasiveness and tumorigenicity for LCNEC, and may be a potential target for LCNEC without standard therapy.

AB - Tropomyosin-related kinase B (TrkB) plays an important role in tumor progression in various kinds of cancers; however, little is known about biological significance of TrkB in human lung cancer, especially large cell neuroendocrine carcinoma (LCNEC). We hereby investigated the expressions of TrkB and its ligand brain-derived neurotrophic factor (BDNF) in clinical specimens and their influences on phenotypes of invasiveness and tumorigenicity for LCNEC. The expressions of TrkB and BDNF analyzed by immunohistochemistry for patients samples with lung cancer (n=104) were significantly higher in neuroendocrine tumor (NET) compared with non-NET. In particular, LCNEC, a subtype of NET, exhibited significantly higher TrkB and BDNF expressions than another NET type: small cell lung cancer (SCLC), and a significant correlation between TrkB and BDNF expressions was noted in LCNEC but not in SCLC. In vitro assay, exogenous BDNF addition enhanced the invasion into matrigels of LCNEC cells, whereas inhibition of TrkB or BDNF suppressed matrix metalloproteinase-2 and -9 activities and the invasiveness. Exogenous BDNF also increased anchor-independent colony formation on soft agar gels for LCNEC, while inhibition of TrkB or BDNF suppressed the anchorage-independency. In vivo experiments, implanted LCNEC cells pretreated with TrkB-siRNA developed no subcutaneous tumor in all six nude mice, although those with control-siRNA formed tumors in four of six nude mice. In conclusion, BDNF/TrkB signal is involved in malignant progression of invasiveness and tumorigenicity for LCNEC, and may be a potential target for LCNEC without standard therapy.

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