TrkB: a neuroblastoma tumor biomarker for theranostic approach

The possibility to combine diagnostics and therapy is the new challenge in biomedical field. Neuroblastoma, the most common and lethal solid tumor in children, exhibits heterogeneous clinical behavior, from spontaneous regression to relentless progression. Current evidence suggests that the TRK family of neurotrophin receptors plays a critical role in these diverse behaviors. Among most common types of TRK receptors, TrkB and its ligand BDNF are highly expressed in aggressive neuroblastoma, and is highly correlated with MYCN amplification, the best-characterized genetic marker of risk in neuroblastoma. Moreover, this tumor overexpresses TrkB and BDNF, resulting in an autocrine or paracrine survival pathway. In this study we analyzed the different expression of TrkB in in LAN5 neuroblastoma cells and in other different tumor cell lines by immunofluorescence, cytofluorometry and Western blot analysis, demonstrating that the full length form of TrkB, is mainly expressed in LAN5 cells. With the aim to inhibit binding of BDNF to TrkB and consequent proliferation cascade activation we synthesized a peptide, called A370, comprising a short BDNF region. After administration of A370 to LAN5 cells, a reduced cell proliferation was detected. Our results indicate that TrkB could be a good diagnostic and therapeutic biomarker for neuroblastoma tumor. Future perspective consider to bulding up nanosystems loaded with A370 for theranostics approach. The research was supported by MIUR, Flagship Project NanoMAX