Harald Stephan and Johannes L. Zakrzewski contributed equally to this work.
Neurotrophin receptor expression in human primary retinoblastomas and retinoblastoma cell lines†
Article first published online: 31 OCT 2007
Copyright © 2007 Wiley-Liss, Inc.
Pediatric Blood & Cancer
Volume 50, Issue 2, pages 218–222, February 2008
How to Cite
Stephan, H., Zakrzewski, J. L., Bölöni, R., Grasemann, C., Lohmann, D. R. and Eggert, A. (2008), Neurotrophin receptor expression in human primary retinoblastomas and retinoblastoma cell lines. Pediatr. Blood Cancer, 50: 218–222. doi: 10.1002/pbc.21369
- Issue published online: 4 DEC 2007
- Article first published online: 31 OCT 2007
- Manuscript Accepted: 14 AUG 2007
- Manuscript Received: 27 JUL 2005
- Deutsche Forschungsgemeinschaft (DFG)
- neurotrophin receptors;
- tyrosine kinase inhibitor
Neurotrophin receptor signaling regulates proliferation, differentiation and death of neuronal cells. Expression of Trk receptors has been implicated in the pathogenesis and prognosis of embryonal tumors, including neuroblastoma, nephroblastoma, and medulloblastoma.
We analyzed TrkA, TrkB, TrkC, and p75 expression using semi-quantitative RT-PCR in 23 retinoblastomas and 8 retinoblastoma cell lines. Comparison of mRNA expression with clinical variables as well as the proliferation (PI) and apoptotic index (AI) of the tumor, was performed by Pearson correlation analysis and two-sample t-test.
Almost all tumor samples and cell lines demonstrated high expression of all Trk receptors. Expression of TrkB and its ligand, BDNF, was most pronounced, suggesting TrkB to be the major Trk receptor involved in retinoblastoma biology. In contrast, p75 expression was substantially reduced in a subset of tumors and cell lines, in particular compared to its expression in normal retina. Tumors with infiltrative growth demonstrated significantly lower relative levels of TrkC expression than localized tumors (P = 0.004). High expression of TrkA was associated with a higher AI (P = 0.04), and high expression of TrkC was associated with a younger age of the patients (P = 0.03). Inhibition of Trk signaling by K252a resulted in marked growth inhibition of retinoblastoma cells in vitro.
Our findings suggest a role for neurotrophin signaling in the biology of retinoblastoma. General Trk inhibitors are effective in decreasing growth rates of retinoblastoma cells in vitro, and should be evaluated in in vivo studies. Pediatr Blood Cancer 2008;50:218–222. © 2007 Wiley-Liss, Inc.