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

Seiichi Odate1, Katsuya Nakamura, Hideya Onishi

  • 1Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Lung Cancer (Amsterdam, Netherlands)
|January 15, 2013
PubMed

Insights

Brain-derived neurotrophic factor (BDNF) and Tropomyosin-related kinase B (TrkB) signaling promotes large cell neuroendocrine carcinoma (LCNEC) invasiveness and tumor growth. Inhibiting BDNF/TrkB may offer a new therapeutic strategy for LCNEC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Tropomyosin-related kinase B (TrkB) is implicated in various cancers.
  • The role of TrkB and its ligand, brain-derived neurotrophic factor (BDNF), in human large cell neuroendocrine carcinoma (LCNEC) remains largely unexplored.

Purpose of the Study:

  • To investigate the expression of TrkB and BDNF in LCNEC.
  • To determine the impact of TrkB and BDNF on LCNEC invasiveness and tumorigenicity.

Main Methods:

  • Immunohistochemistry was used to analyze TrkB and BDNF expression in 104 lung cancer patient samples.
  • In vitro assays assessed the effects of BDNF and TrkB inhibition on LCNEC cell invasion and anchorage-independent growth.
  • In vivo experiments utilized TrkB-siRNA in nude mice to evaluate tumor formation.

Main Results:

  • TrkB and BDNF expression were significantly higher in neuroendocrine tumors (NETs), particularly LCNEC, compared to non-NETs and small cell lung cancer (SCLC).
  • A correlation between TrkB and BDNF was observed in LCNEC.
  • Exogenous BDNF enhanced LCNEC cell invasion and anchorage-independent growth, while TrkB or BDNF inhibition suppressed these phenotypes and matrix metalloproteinase activity.
  • TrkB-siRNA pretreatment prevented tumor formation in vivo.

Conclusions:

  • The BDNF/TrkB signaling pathway is integral to the malignant progression of LCNEC.
  • Targeting the BDNF/TrkB pathway presents a potential therapeutic strategy for LCNEC, a cancer lacking standard treatments.

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