BDNF mediated TrkB activation is a survival signal for transitional cell carcinoma cells

  • Authors:
    • Yen Ta Huang
    • Pei Chun Lai
    • Chia Chen Wu
    • Shih Hsin Hsu
    • Chuan Chu Cheng
    • Yi Fan Lan
    • Ted H. Chiu
  • View Affiliations

  • Published online on: June 1, 2010     https://doi.org/10.3892/ijo_00000633
  • Pages: 1469-1476
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Abstract

Pathologically, >90% of bladder cancer is transitional cell carcinoma (TCC). Previously, brain-derived neurotrophic factor (BDNF) but not tropomyosin-related kinase B (TrkB) was found in normal urothelium. TrkB activation by BDNF has been shown to promote the progression of several cancers, however, the existence and functional roles of both BDNF and TrkB in TCC have not been elucidated. In this study, three human TCC cell lines, BFTC905, TSGH8301, and T24 were used for the investigation. Both BDNF and TrkB but not TrkA or TrkC identified by RT-PCR and Western blotting were found in these cell lines. Immunostaining demonstrated the cytosolic expression of BDNF and TrkB, as well as membranous expression of TrkB in these cells. BDNF released from three cell lines was also detected in culture medium by ELISA. The proliferation of BFTC905 cells was enhanced by recombinant human BDNF (rhBDNF) in vitro, which was associated with increased phospho-TrkB and phospho-ERK levels. In contrast, TrkB-Fc chimeric protein served as BDNF scavenger eliciting cytotoxicity. Addition of rhBDNF in these cell lines cultured in poly-HEMA [Poly(2-hydroxyethyl methacrylate)] coated dishes for 48 h did not confer resistance to anoikis. Increased phospho-Akt expression was observed transiently within an hour after rhBDNF administration but disappeared 24 h later. Weekly injections of 100 ng rhBDNF into the cancer cell-loading site for 6 weeks promoted BFTC905 xenograft growth in SCID mice. Daily injection of 5 µg TrkB-Fc chimeric protein into the tumor 2 weeks after tumor cell implantation delayed tumor growth concomitant with phospho-TrkB suppression in xenografts. These results indicate that BDNF binding to TrkB receptor is a survival signal for TCC cells. Drugs that block BDNF or TrkB may provide a new and potential approach for TCC therapy.

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June 2010
Volume 36 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Huang YT, Lai PC, Wu CC, Hsu SH, Cheng CC, Lan YF and Chiu TH: BDNF mediated TrkB activation is a survival signal for transitional cell carcinoma cells. Int J Oncol 36: 1469-1476, 2010.
APA
Huang, Y.T., Lai, P.C., Wu, C.C., Hsu, S.H., Cheng, C.C., Lan, Y.F., & Chiu, T.H. (2010). BDNF mediated TrkB activation is a survival signal for transitional cell carcinoma cells. International Journal of Oncology, 36, 1469-1476. https://doi.org/10.3892/ijo_00000633
MLA
Huang, Y. T., Lai, P. C., Wu, C. C., Hsu, S. H., Cheng, C. C., Lan, Y. F., Chiu, T. H."BDNF mediated TrkB activation is a survival signal for transitional cell carcinoma cells". International Journal of Oncology 36.6 (2010): 1469-1476.
Chicago
Huang, Y. T., Lai, P. C., Wu, C. C., Hsu, S. H., Cheng, C. C., Lan, Y. F., Chiu, T. H."BDNF mediated TrkB activation is a survival signal for transitional cell carcinoma cells". International Journal of Oncology 36, no. 6 (2010): 1469-1476. https://doi.org/10.3892/ijo_00000633