188P - Tropomyosin-related kinase B is a therapeutic target and prognostic factor for aggressive lung cancer including LCNEC

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Lung and other Thoracic Tumours
Translational Research
Presenter Seiichi Odate
Authors S. Odate1, K. Nakamura2, H. Onishi3, A. Uchiyama4, M. Kato5, M. Tanaka2, M. Katano3
  • 1Department Of Cancer Therapy And Research, Kyushu University, 8128582 - Fukuoka/JP
  • 2Surgery And Oncology, Kyushu University, Fukuoka/JP
  • 3Cancer Therapy And Research, Kyushu University, 8128582 - Fukuoka/JP
  • 4Surgery, Kyushu Kosei Nenkin Hospital, Fukuoka/JP
  • 5Surgery, Hamanomachi Hospital, Fukuoka/JP

Abstract

Background

Lung cancer is one of the most common types of cancer, accounting for more deaths than any other types of cancer. Tropomyosin-related kinase B (TrkB) has previously been shown to be important in tumor progression in neuroblastoma, pancreatic cancer, and prostate cancer. However, little is known about biological significance of TrkB in human lung cancer. Here we investigate if TrkB may be a therapeutic target and prognostic factor for lung cancer.

Methods

Surgically resected specimen; The expression of TrkB and its ligand BDNF (Brain-derived neurotrophic factor) were investigated in 104 patients with primary lung cancers (8 small cell carcinomas, 11 large cell neuroendocrine carcinomas, 10 large cell carcinomas, 20 adenocarcinomas, 55 squamous cell carcinomas) by immunohistochemical staining. In vitro assay; Large cell neuroendocrine carcinoma (LCNEC) cell lines (NCI-H460 and NCI-H810) expressing TrkB were used. TrkB-siRNA and TrkB tyrosine kinase inhibitor (K252a) were used to inhibit TrkB. BDNF-siRNA was used to inhibit BDNF. Cell proliferation and invasion were evaluated by MTT and Transwell assays, respectively.

Results

1) There were significantly higher TrkB and BDNF expressions in LCNEC cases than any other histological types. LCNEC cases also had poorer prognosis than any other histological types. 2) Higher expression of TrkB positively correlated with disease free survival (p < 0.001) and overall survival (p < 0.05) in all histological types. 3) BDNF upregulated the invasion of LCNEC cell lines. 4) Knockdown of TrkB or BDNF mRNA expression using siRNA significantly decreased the invasion of LCNEC cell lines. K252a also significantly decreased the invasion of LCNEC cell lines.

Conclusions

These data suggests that BDNF/TrkB signal is important in LCNEC and TrkB is a potential therapeutic target and prognostic factor for aggressive lung cancer including LCNEC.

Disclosure

All authors have declared no conflicts of interest.